# ent

id: cord-275225-fvq8hezk
type: DNA
entity:
  Ákos Bálint Ádám Farsang Attila Balka Gyula Hakhverdyan Mikhayil Rasmussen Thomas Bruun Blomberg Jonas Belák Sándor title


id: cord-263165-bv4dh9eu
type: EVENT
entity:
  Transmissible Gastroenteritis Virus TGEV Porcine Epidemic Diarrhea Virus PEDV and Hemagglutinating Encephalomyelitis Virus


id: cord-267014-3vi7pgvr
type: PROTEIN
entity:
  FIPV 6b protein Canine coronavirus CCV feline enteric coronavirus FECV feline infectious peritonitis virus


id: cord-299342-l8ugjou9
type: PROTEIN
entity:
  Mr 58 000 5 12 c o m p l e m e n t fixation 1 12 gel diffusion 1 immunofluorescence IFT 12 13 15 enzyme


id: cord-280621-tph5n7ak
type: ORG
entity:
  Veterinary Immunology and Immunopathology Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency EasyModeller


id: cord-269986-jdcw59r2
type: GGP
entity:
  p38 c Jun N terminal mitogen activated protein kinase pathways and activates transcription factor AP 1 Leptin


id: cord-283739-p7b4mtbl
type: DISEASE
entity:
  acute respiratory syndrome coronavirus SARS CoV Middle East respiratory syndrome coronavirus MERS CoV


id: cord-291858-e0s3o2r4
type: PROTEIN
entity:
  feline C type lectin dendritic cell specific intercellular adhesion molecule 3 grabbing nonintegrin fDC


id: cord-287157-6rwevq39
type: PROTEIN
entity:
  IFN gamma Murine coronavirus induced subacute fatal peritonitis in C57BL 6 mice deficient in gamma interferon


id: cord-287157-6rwevq39
type: ORG
entity:
  the Center for Companion Animal Health Center CCAH School of Veterinary Medicine University of California Davis CA USA 95616


id: cord-276617-chgjpg0v
type: PROTEIN
entity:
  Netherlands Phycoerythrin PE conjugated anti CD21 monoclonal antibody MAb anti canine CD21 homologue


id: cord-292908-rbn3foj3
type: PROTEIN
entity:
  immunogen 25 MAbs F2 1 F29 1 F16 4 F18 2 F19 1 F30 1 F34 1 F35 2 F36 1 F41 1 F51 1 F52 1 F70 2 F75 3 F15 2 F24 1 F25 1 F46 4 F49 1 F69 3 F80 1 F6 3 F22 3 F23 2 F50 4


id: cord-292908-rbn3foj3
type: CHEMICAL
entity:
  F34 1 F35 2 F36 1 F41 1 F51 1 F52 1 F70 2 F75 3 F15 2 F24 1 F25 1 F46 4 F49 1 F69 3 F80 1 F6 3 F22 3 F23 2 F50


id: cord-283132-rfw8njpo
type: DISEASE
entity:
  encephalomyelitis virus HIV human immunodeficiency virus HRSV human respiratory syncytial virus IBV infectious bronchitis


id: cord-293565-420thmsr
type: ORG
entity:
  the National Institute of Allergy and Infectious Diseases National Institutes of Health Department of Health and Human Services


id: cord-293565-420thmsr
type: ORG
entity:
  the Virology Division Department of Infectious Diseases and Immunology Veterinary Faculty Utrecht University


id: cord-322629-kv83ekg0
type: DNA
entity:
  primer positions 876 895 5 CAACTGGGGAGATGAACCTT 3 antisense primer positions 1644 1663 5 GGTAGCATTTGGCAGCGTTA 3


id: cord-322629-kv83ekg0
type: CHEMICAL
entity:
  N gene sense primer positions 876 895 5 CAACTGGGGAGATGAACCTT 3 antisense primer positions 1644 1663 5 GGTAGCATTTGGCAGCGTTA 3 PCR


id: cord-311625-d7iycdyh
type: DNA
entity:
  5 untranslated region 5 UTR Open Reading Frames ORFs 1a and 1b and 3 untranslated region 3 UTR Table 1


id: cord-309205-l8vjtrjq
type: DISEASE
entity:
  critically distinguishing feature between the two feline coronavirus FCoV pathotypes feline enteric coronavirus FECV


id: cord-336639-jaue41mv
type: DISEASE
entity:
  gastroenteritis coronavirus nucleocapsid protein gene Histopathological alterations of lymphatic tissues


id: cord-312006-c08u4t16
type: PROTEIN
entity:
  coronavirus Clostridium perfringens enterotoxin A Cryptosporidium spp Giardia spp Cystoisospora spp hookworms ascarids Salmonella spp astrovirus feline panleukopenia virus calicivirus and Spirometra spp Interestingly cats with diarrhea were


id: cord-312006-c08u4t16
type: TAXON
entity:
  coronavirus Clostridium perfringens enterotoxin A Cryptosporidium spp Giardia spp Cystoisospora spp hookworms ascarids Salmonella spp astrovirus feline panleukopenia virus calicivirus


id: cord-351955-9l4786lb
type: ORG
entity:
  the Center for Companion Animal Health School of Veterinary Medicine University of California Davis CA


id: cord-348204-365z3qxz
type: GGP
entity:
  TNF α and IFN γ expressions 9 26 Based on previous studies on the growth of FIPV 79 1146 in CRFK cells


# bib

id: cord-023053-j061ywrl
title: Cats, coronaviruses and coronavirus antibody tests
author: BARLOUGH, J. E.
date: 2008-04-10
txt: ./txt/cord-023053-j061ywrl.txt
cache: ./cache/cord-023053-j061ywrl.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166406/
doi: 10.1111/j.1748-5827.1985.tb02210.x
summary:
  In domestic and exotic cats, FIPV is the aetiologic agent of a lethal disease-feline infectious peritonitis (FIP)-characterized by fibrinous serositis, vasculitis, and formation of disseminated pyogranulomas (Wolfe & Griesemer. Laboratory test procedures for detection of coronavirus antibody in feline sera include biological assays such as virus neutralization (VN); non-biological, immunochemical techniques such as indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), and kinetics-based ELISA (KELA); and other methods such as agar gel immunodiffusion and passive haemagglutination , though the availability of such tests varies worldwide. The serodiagnostic potential of these assays (i.e., their ability to identify cats with active FIP and/or potential virus carriers/excretors) is thus limited not only by the widespread distribution of serum coronavirus antibody in the feline population, but also by the possibility that non-FIPV coronaviruses may be responsible for some of the seroconversions that they detect.

abstract:
  Feline infectious peritonitis and other coronavirus infections of cats are briefly reviewed. Interpretation and applications of feline coronavirus antibody tests are described, and general recommendations are provided for practitioners. Some of the major unresolved questions regarding coronavirus infections of cats are delineated.


id: cord-254291-y8xvh6hs
title: Nucleotide Sequence of the Inter-Structural Gene Region of Feline Infectious Peritonitis Virus
author: Yamanaka, Miles
date: 1998
txt: ./txt/cord-254291-y8xvh6hs.txt
cache: ./cache/cord-254291-y8xvh6hs.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/9654687/
doi: 10.1023/a:1008099209942
summary:
  The sequence of the region located between the S and M glycoprotein genes of the 79-1146 strain of feline infectious peritonitis virus (FIPV) is presented. The inter-structural gene region encodes 3 open reading frames (ORFs), termed ORFs 3a, 3b and 4, with nucleotide sequences conforming to the minimum conserved transcription signal upstream of each. The FIPV interstructural gene region is identical in length when compared to the Insavc-1 strain of canine coronavirus (CCV) but differs from various strains of transmissible gastroenteritis virus (TGEV) by the presence of deletions and insertions. This inter-structural gene region has been examined in the related coronaviruses transmissible gastroenteritis virus (TGEV) and canine coronavirus (CCV) (2±6). The arrangement of the open reading frames (ORFs) in the inter-structural gene region has been described for the FIPV genome (1,7), but detailed sequence has not been presented. The sequence identity between FIPV 79-1146 and the Purdue strain of TGEV in the inter-structural gene region is 90.7%.

abstract:
  The sequence of the region located between the S and M glycoprotein genes of the 79-1146 strain of feline infectious peritonitis virus (FIPV) is presented. The inter-structural gene region encodes 3 open reading frames (ORFs), termed ORFs 3a, 3b and 4, with nucleotide sequences conforming to the minimum conserved transcription signal upstream of each. An additional ORF, 3x, partially overlaps the 3′ end of ORF 3a. The FIPV interstructural gene region is identical in length when compared to the Insavc-1 strain of canine coronavirus (CCV) but differs from various strains of transmissible gastroenteritis virus (TGEV) by the presence of deletions and insertions. The sizes of ORF 3a and 4 are conserved in FIPV, TGEV and CCV. However, as with CCV, the FIPV ORF 3b is truncated in comparison with TGEV.


id: cord-255873-18zmvlmk
author: Wang, Jinshan
date: 2014-11-14
txt: ./txt/cord-255873-18zmvlmk.txt
cache: ./cache/cord-255873-18zmvlmk.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1107/s2053230x14022390
doi: 10.1107/s2053230x14022390
summary:
  title: Crystallization and preliminary crystallographic study of Feline infectious peritonitis virus main protease in complex with an inhibitor In this study, the main protease of FIPV in complex with a Michael acceptor-type inhibitor was crystallized. The complex crystals diffracted to 2.5 Å resolution and belonged to space group I422, with unit-cell parameters a = 112.3, b = 112.3, c = 102.1 Å. On the other hand, FIPV efficiently replicates in macrophages/monocytes, leading to feline infectious peritonitis (FIP), a highly lethal systemic granulomatous disease of wild and domestic cats (Addie et al., 2009; Pedersen, 2009; Balint, Farsang, Szeredi et al., 2014; Kipar & Meli, 2014) . Isopropyl -d-1-thiogalactopyranoside was then added to a final concentration of 0.5 mM and the cultures were induced to express FIPV main protease at 289 K for 16 h. A typical diffraction pattern of an FIPV main protease complex crystal collected on beamline BL17U of the Shanghai Synchrotron Radiation Facility (SSRF).

title:
  Crystallization and preliminary crystallographic study of Feline infectious peritonitis virus main protease in complex with an inhibitor

abstract:
  Feline infectious peritonitis virus (FIPV) causes a lethal systemic granulomatous disease in wild and domestic cats around the world. Currently, no effective vaccines or drugs have been developed against it. As a member of the genus Alphacoronavirus, FIPV encodes two polyprotein precursors required for genome replication and transcription. Each polyprotein undergoes extensive proteolytic processing, resulting in functional subunits. This process is mainly mediated by its genome-encoded main protease, which is an attractive target for antiviral drug design. In this study, the main protease of FIPV in complex with a Michael acceptor-type inhibitor was crystallized. The complex crystals diffracted to 2.5 Å resolution and belonged to space group I422, with unit-cell parameters a = 112.3, b = 112.3, c = 102.1 Å. There is one molecule per asymmetric unit.


id: cord-257974-kllqjn68
author: Woods, Roger D.
date: 1988
txt: ./txt/cord-257974-kllqjn68.txt
cache: ./cache/cord-257974-kllqjn68.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32214595/
doi: 10.1007/bf01404139
summary:
  title: Cultivation techniques for animal coronaviruses: Emphasis on feline infectious peritonitis virus, canine coronavirus, transmissible gastroenteritis virus, and porcine hemagglutinating encephalomyelitis virus Generally these viruses infect epithelial cells of the respiratory tract [human coronavirus (HCV), infectious bronchitis virus (IBV), rat coronavirus (RCV), porcine respiratory coronavirus (PCV)] and epithelial cells of the gastrointestinal tract [bovine coronavirus (BCV), canine eoronavirus (CCV), transmissible gastroenteritis virus {TGEV), turkey coronavirus (TCV), feline enteric coronavirus (FECV), human enteric coronavirus (HECV)]. In addition to CRFK cells, a fetal cat whole fibroblast (FCWF) cell line will support the growth of FIPV, as well as FECV, CCV, and TGEV (28,43t, and corn-Journal of Tissue Culture Methods Vol. 11, No. 2, 1988 parison of antigenic and serologic relatedness of the enteric coronaviruses was done in this cell line ~43). This cell line can be used for primary isolation of virus from clinical specimens and in vitro growth of TGEV It0}.

title:
  Cultivation techniques for animal coronaviruses: Emphasis on feline infectious peritonitis virus, canine coronavirus, transmissible gastroenteritis virus, and porcine hemagglutinating encephalomyelitis virus

abstract:
  Techniques are described for the growth and characterization of some mammalian coronaviruses. Because of the fastidious nature of their growth requirements, most will replicate only in cells derived from the natural host or a closely related species. Fetal cat cells are used to grow FIPV, and porcine cells are used to grow TGEV and HEV. However, CCV will replicate in both feline and canine cells. Although all four of these viruses prefer to replicate in a cell in the stationary phase of growth, FIPV is able to replicate in an actively growing cell. Each virus causes a cytopathic effect in monolayer cell cultures under agar or media 18 to 72 h postinfection. Primary isolation of each virus from field specimens is difficult, although most can usually be isolated after 1 to 3 blind passages in the cell culture.


id: cord-258374-qht98q0l
author: Takano, Tomomi
date: 2009-04-03
txt: ./txt/cord-258374-qht98q0l.txt
cache: ./cache/cord-258374-qht98q0l.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s00705-009-0371-3
doi: 10.1007/s00705-009-0371-3
summary:
  title: Neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF) produced by macrophages in cats infected with feline infectious peritonitis virus contribute to the pathogenesis of granulomatous lesions Furthermore, it was investigated whether macrophages, one of the target cells of FIPV infection, produce neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF). The neutrophil survival rates were significantly increased in the presence of the culture supernatant of macrophages infected with the mixture of FIPV and MAb 6-4-2 compared to those in the presence of other supernatants (Fig. 5) . When SPF-cat-derived alveolar macrophages were infected with a mixture of FIPV and MAb 6-4-2, the intracellular TNF-alpha, GM-CSF, and G-CSF mRNA levels increased (Fig. 6 ). These cytokine mRNA levels were also elevated in macrophages infected with FIPV and MAb 6-4-2, clarifying the presence of neutrophil survival factors in the macrophage culture supernatant. It was suggested that: (1) FIPV-infected macrophages release TNF-alpha, GM-CSF, and G-CSF in response to virus replication, and (2) these cytokines act on neutrophils and prolong their survival.

title:
  Neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF) produced by macrophages in cats infected with feline infectious peritonitis virus contribute to the pathogenesis of granulomatous lesions

abstract:
  Feline infectious peritonitis (FIP) is a feline coronavirus (FCoV)-induced fatal disease of domestic and wild cats. The infiltration of neutrophils into granulomatous lesions is unusual for a viral disease, but it is a typical finding of FIP. This study aimed to investigate the reason for the lesions containing neutrophils in cats with FIP. Neutrophils of cats with FIP were cultured, and changes in the cell survival rate were assessed. In addition, the presence or absence of neutrophil survival factors was investigated in specimens collected from cats with FIP. Furthermore, it was investigated whether macrophages, one of the target cells of FIPV infection, produce neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF). We showed that virus-infected macrophages overproduce neutrophil survival factors, and these factors act on neutrophils and up-regulate their survival. These observations suggest that sustained production of neutrophil survival factors by macrophages during FCoV infection is sufficient for neutrophil survival and contributes to development of granulomatous lesions.


id: cord-258684-lq4knxgf
author: Takano, Tomomi
date: 2020-05-24
txt: ./txt/cord-258684-lq4knxgf.txt
cache: ./cache/cord-258684-lq4knxgf.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/v12050576
doi: 10.3390/v12050576
summary:
  Hydroxychloroquine (HCQ) is a drug approved by several countries to treat malaria and immune-mediated diseases in humans, and its antiviral effects on other viral infections (e.g., SARS-CoV-2, dengue virus) have been confirmed. Interestingly, the combination of 100 μM of HCQ and 10(4) U/mL of recombinant feline IFN-ω (rfIFN-ω, veterinary registered drug) increased its antiviral activity against type I FIPV infection. As shown in Figure 4 , type I FIPV replication was significantly inhibited by HCQ and rfIFN-ω, and the combination of these drugs strongly decreased the replication of virus. As shown in Figure 4 , type I FIPV replication was significantly inhibited by HCQ and rfIFN-ω, and the combination of these drugs strongly decreased the replication of virus. As shown in Figure 4 , type I FIPV replication was significantly inhibited by HCQ and rfIFN-ω, and the combination of these drugs strongly decreased the replication of virus.

title:
  Antiviral Effects of Hydroxychloroquine and Type I Interferon on In Vitro Fatal Feline Coronavirus Infection

abstract:
  Feline infectious peritonitis (FIP) is a viral disease with a high morbidity and mortality by the FIP virus (FIPV, virulent feline coronavirus). Several antiviral drugs for FIP have been identified, but many of these are expensive and not available in veterinary medicine. Hydroxychloroquine (HCQ) is a drug approved by several countries to treat malaria and immune-mediated diseases in humans, and its antiviral effects on other viral infections (e.g., SARS-CoV-2, dengue virus) have been confirmed. We investigated whether HCQ in association with interferon-ω (IFN-ω) is effective for FIPV in vitro. A total of 100 μM of HCQ significantly inhibited the replication of types I and II FIPV. Interestingly, the combination of 100 μM of HCQ and 10(4) U/mL of recombinant feline IFN-ω (rfIFN-ω, veterinary registered drug) increased its antiviral activity against type I FIPV infection. Our study suggested that HCQ and rfIFN-ω are applicable for treatment of FIP. Further clinical studies are needed to verify the combination of HCQ and rIFN-ω will be effective and safe treatment for cats with FIP.


id: cord-263165-bv4dh9eu
title: Coronaviridae, pathogenetic and clinical aspects: An update
author: Möstl, Karin
date: 1990-12-31
txt: ./txt/cord-263165-bv4dh9eu.txt
cache: ./cache/cord-263165-bv4dh9eu.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/1963836/
doi: 10.1016/0147-9571(90)90085-8
summary:
  The recent detection of previously unknown coronaviruses or mutants, like the "Porcine Epidemic Diarrhea"-virus (PEDV) and the TGE-like "Porcine Respiratory Coronavirus" (PRCV) on one hand and new knowledge about pathogenetic mechanisms, for example in FIPV-infections, on the other hand are the basis for this review article. For diagnosis TGEV antigen can be detected by immunofluorescence in the small intestine of piglets at an early stage of disease, by virus isolation in tissue culture or by ELISA. As it causes a respiratory infection and does not replicate in the enteric tract, it was named "Respiratory Variant" of TGEV [16] and recently "Porcine respiratory coronavirus". Pedersen [51] assumed that not only the properties of the infecting virus strain were responsible for the outcome of the disease, but that also the immunologic situation of the host and the type and degree of developing immunity may be of great importance. Natural infection with the Porcine Respiratory Coronavirus induces protective lactogenic immunity against Transmissible Gastroenteritis

abstract:
  Abstract A review is given about pathogenetic and clinical aspects of the well-known as well as of recently detected members of the family Coronaviridae. Special attention is paid to coronavirus infections of domestic cattle and pets, whereas avian, murine, rat and human coronaviruses are summarized briefly.


id: cord-267014-3vi7pgvr
title: Genomic organization and expression of the 3′ end of the canine and feline enteric coronaviruses
author: Vennema, H.
date: 1992-11-30
txt: ./txt/cord-267014-3vi7pgvr.txt
cache: ./cache/cord-267014-3vi7pgvr.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/004268229290174N
doi: 10.1016/0042-6822(92)90174-n
summary:
  Abstract The genomic organization at the 3′ end of canine coronavirus (CCV) and feline enteric coronavirus (FECV) was determined by sequence analysis and compared to that of feline infectious peritonitis virus (FIPV) and transmissible gastroenteritis virus (TGEV) of swine. Amplification of cDNA was performed by the polymerase chain reaction (PCR) as described (Kawasaki and Wang, 1989) , after the addition of synthetic oligonucleotide 178, 5''-GATGACACACAGGlTGAG-3'', which is identical to the carboxyl-terminus of the nucleocapsid (N) protein gene of FIPV (nucleotides 1945-l 962; Vennema et a/., 1991) . The nucleotide sequences flanking the ORFs 6a and 6b of FIPV and CCV and ORF 7 of TGEV were aligned to design primers for cDNA synthesis and polymerase chain reaction (PCR) amplification. The recombinant expression products were compared to the proteins produced in CCV-, FECV-, and FIPV-infected cells, which were analyzed similarly (Fig. 6) .

abstract:
  Abstract The genomic organization at the 3′ end of canine coronavirus (CCV) and feline enteric coronavirus (FECV) was determined by sequence analysis and compared to that of feline infectious peritonitis virus (FIPV) and transmissible gastroenteritis virus (TGEV) of swine. Comparison of the latter two has previously revealed an extra open reading frame (ORF) at the 3′ end of the FIPV genome, lacking in TGEV, which is currently designated ORF 6b. Both CCV and FECV possess 6b-related ORFs at the 3′ ends of their genomes. The presence of ORF 6b in three of four viruses in this antigenic cluster strongly suggests that TGEV has lost this ORF by deletion. The CCV ORF 6b is collinear with that of FIPV, but the predicted amino acid sequences are only 58% identical. The FECV ORF 6b contains a large deletion compared to that of FIPV, reducing the collinear part to 60%. The sequence homologies were highest between CCV and TGEV on the one hand and between FECV and FIPV on the other. Previously, we showed that the expression product of the FIPV ORF 6b can be detected in infected cells by immunoprecipitation (Vennema et al., 1992). In the present study we have performed similar experiments with CCV and FECV. In infected cells both viruses produced proteins related to but different from the FIPV 6b protein.


id: cord-269986-jdcw59r2
author: Regan, Andrew D.
date: 2009-02-05
txt: ./txt/cord-269986-jdcw59r2.txt
cache: ./cache/cord-269986-jdcw59r2.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0042682208007356
doi: 10.1016/j.virol.2008.11.006
summary:
  Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors. To determine whether viral replication was required for FIPV-induced p38 MAPK activation, UV-inactivated virus was added to PFBM cells and analyzed by western blot as described above (Fig. 1B) . Overall these data indicate that production of the pro-inflammatory cytokine TNF-alpha in FIPVinfected PFBM cells is regulated by activation of the p38 MAPK pathway. In this study we show that infection by FIPV causes a rapid activation the p38 MAPK pathway in PFBM cells, and that this process directly regulates production of the pro-inflammatory cytokines TNF-alpha and IL-1 beta.

title:
  Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells

abstract:
  Feline infectious peritonitis (FIP) is an invariably fatal disease of cats caused by systemic infection with a feline coronavirus (FCoV) termed feline infectious peritonitis virus (FIPV). The lethal pathology associated with FIP (granulomatous inflammation and T-cell lymphopenia) is thought to be mediated by aberrant modulation of the immune system due to infection of cells such as monocytes and macrophages. Overproduction of pro-inflammatory cytokines occurs in cats with FIP, and has been suggested to play a significant role in the disease process. However, the mechanism underlying this process remains unknown. Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation and pro-inflammatory cytokine production was inhibited by the pyridinyl imidazole inhibitors SB 203580 and SC 409 in a dose-dependent manner. FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors.


id: cord-271831-vekok62k
title: Replication of feline coronaviruses in peripheral blood monocytes
author: Dewerchin, H. L.
date: 2005-08-01
txt: ./txt/cord-271831-vekok62k.txt
cache: ./cache/cord-271831-vekok62k.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16052283/
doi: 10.1007/s00705-005-0598-6
summary:
  Feline infectious peritonitis virus (FIPV) (Coronaviridae) causes the most lethal viral infection in cats: FIP. In this study, infection kinetics (titres and antigen expression) of FIPV 79-1146, and FECV 79-1683, were determined in peripheral blood monocytes from 3 donor cats and compared to those in Crandell feline kidney (CrFK) cells. Two coronaviruses are described in cats: feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV). Within this population of 19 cats, the monocytes isolated from 9 cats showed a continuous increase in viral antigen positive cells during a 24 hour time span after inoculation with FIPV. Monocytes from 9 cats did not sustain both FIPV and FECV infection since the number of viral antigen positive cells dropped after 6 or 12 hpi (third pattern). In an infection kinetics study where another cell type, feline peritoneal macrophages, was used, different results in the antigen expression kinetics were obtained [29] .

abstract:
  Feline infectious peritonitis virus (FIPV) (Coronaviridae) causes the most lethal viral infection in cats: FIP. The related feline enteric coronavirus (FECV) causes mild enteritis. Why these feline coronaviruses manifest so differently in vivo is not known. In this study, infection kinetics (titres and antigen expression) of FIPV 79-1146, and FECV 79-1683, were determined in peripheral blood monocytes from 3 donor cats and compared to those in Crandell feline kidney (CrFK) cells. The infection kinetics in monocytes were host dependent. Monocytes from 1 cat were resistant to both FIPV- and FECV-infection. Monocytes from the other 2 cats could initially be infected by both FIPV and FECV but FIPV infection was sustained in monocytes of only one cat. FECV-infection was never sustained and viral production was up to 100 times lower than in FIPV-infected monocytes. In CrFK cells, FIPV and FECV infection kinetics did not differ. In monocytes of a larger cat population (n = 19) the 3 infection patterns were also found. Considering all 22 investigated cats, 3/22 were not susceptible for FIPV and FECV. The rest could be infected with FECV and FIPV but 10/22 cats had monocytes that only sustained FIPV infection and 9/22 sustained neither FIPV nor FECV infection.


id: cord-274673-tjzlssal
author: De Groot, Raoul J.
date: 1989-08-31
txt: ./txt/cord-274673-tjzlssal.txt
cache: ./cache/cord-274673-tjzlssal.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/2548329/
doi: 10.1016/0042-6822(89)90619-3
summary:
  authors: De Groot, Raoul J.; Van Leen, Robert W.; Dalderup, Mieke J.M.; Vennema, Harry; Horzinek, Marian C.; Spaan, Willy J.M. title: Stably expressed FIPV peplomer protein induces cell fusion and elicits neutralizing antibodies in mice Abstract We have established bovine papilloma virus (BPV)-transformed mouse C127 cell lines that synthesize the peplomer protein of the feline infectious peritonitis virus (FIPV) strain 79-1146. Mice immunized with whole lysates of the transformed cells produced FIPV-neutralizing antibodies as shown by plaque reduction. Mammalian cell lines expressing the FIPV peplomer gene would provide a convenient source of protein to dissect the role of E2 in FIP. It is shown that the expression product induces fusion of FIPV-permissive feline cells and is immunogenic in mice. (b) Glyoxal-denatured RNA extracted from noninduced (lane 2) and heat-shock-induced (lane 3) RM(-)I 7 cells was separated on 0.8% agarose gels, transferred to a nylon membrane, and hybridized to a nick-translated 4.5-kbBamHl fragment containing the complete FIPV E2 gene.

title:
  Stably expressed FIPV peplomer protein induces cell fusion and elicits neutralizing antibodies in mice

abstract:
  Abstract We have established bovine papilloma virus (BPV)-transformed mouse C127 cell lines that synthesize the peplomer protein of the feline infectious peritonitis virus (FIPV) strain 79-1146. For this purpose, a new cassette expression vector pHSL, which carries the Drosophila HSp70 promotor and the polyadenylation signal of the Moloney murine leukemia virus long terminal repeat, was constructed. Cocultivation of the BPV-transformed cell lines with FIPV-permissive feline fcwf-D cells resulted in polykaryocyte formation. Since it depended on the presence of fcwf-D cells, binding of E2 to the cell receptor may be required for membrane fusion. E2 was synthesized as a core-glycosylated protein of 180K which was only slowly transported from the endoplasmic reticulum to the medial Golgi: of the E2-molecules labeled during a 1-hr pulse about half was still completely sensitive to endoglycosidase H after a 2-hr chase, while the remaining E2 had been chased into multiple, partially endoglycosidase H-resistant forms. Immunofluorescence studies also indicated that most E2 was retained intracellularly. Mice immunized with whole lysates of the transformed cells produced FIPV-neutralizing antibodies as shown by plaque reduction.


id: cord-275225-fvq8hezk
author: Hornyák, Ákos
date: 2012-02-18
txt: ./txt/cord-275225-fvq8hezk.txt
cache: ./cache/cord-275225-fvq8hezk.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0166093412000365
doi: 10.1016/j.jviromet.2012.01.022
summary:
  The quantitative sg-mRNA detection method revealed more than 10-50,000 times increase of the M gene sg-mRNA in organ materials of feline infectious peritonitis cases, compared to those of the enteric FCoV variants present in the faeces of normal, healthy cats. The quantitative sg-mRNA detection method revealed more than 10-50,000 times increase of the M gene sg-mRNA in organ materials of feline infectious peritonitis cases, compared to those of the enteric FCoV variants present in the faeces of normal, healthy cats. These results indicate the applicability of the new P-sg-QPCR test as a powerful novel tool for the better detection and quantitation of FCoV and for the improved diagnosis of feline infectious peritonitis, this important disease of the Felidae, causing serious losses in the cat populations at a global scale. The detailed analysis of the feline infectious peritonitis positive cat samples by SYBR-Green QPCR method revealed that the following organs harbour FCoV most frequently: lungs 6/6 (100%), liver 6/6 (100%), kidney 10/11 (90.9%), mesenteric lymph node 18/20 (90%), spleen 16/20 (80%) and gut 15/10 (66.7%).

title:
  Detection of subgenomic mRNA of feline coronavirus by real-time polymerase chain reaction based on primer-probe energy transfer (P-sg-QPCR)

abstract:
  Feline infectious peritonitis is one of the most severe devastating diseases of the Felidae. Upon the appearance of clinical signs, a cure for the infected animal is impossible. Therefore rapid and proper diagnosis for both the presence of the causative agent, feline coronavirus (FCoV) and the manifestation of feline infectious peritonitis is of paramount importance. In the present work, a novel real-time RT-PCR method is described which is able to detect FCoV and to determine simultaneously the quantity of the viral RNA. The new assay combines the M gene subgenomic messenger RNA (sg-mRNA) detection and the quantitation of the genome copies of FCoV. In order to detect the broadest spectrum of potential FCoV variants and to achieve the most accurate results in the detection ability the new assay is applying the primer-probe energy transfer (PriProET) principle. This technology was chosen since PriProET is very robust to tolerate the nucleotide substitutions in the target area. Therefore, this technology provides a very broad-range system, which is able to detect simultaneously many variants of the virus(es) even if the target genomic regions show large scale of variations. The detection specificity of the new assay was proven by positive amplification from a set of nine different FCoV strains and negative from the tested non-coronaviral targets. Examination of faecal samples of healthy young cats, organ samples of perished animals, which suffered from feline infectious peritonitis, and cat leukocytes from uncertain clinical cases were also subjected to the assay. The sensitivity of the P-sg-QPCR method was high, since as few as 10 genome copies of FCoV were detected. The quantitative sg-mRNA detection method revealed more than 10–50,000 times increase of the M gene sg-mRNA in organ materials of feline infectious peritonitis cases, compared to those of the enteric FCoV variants present in the faeces of normal, healthy cats. These results indicate the applicability of the new P-sg-QPCR test as a powerful novel tool for the better detection and quantitation of FCoV and for the improved diagnosis of feline infectious peritonitis, this important disease of the Felidae, causing serious losses in the cat populations at a global scale.


id: cord-276617-chgjpg0v
author: Takano, Tomomi
date: 2008-11-30
txt: ./txt/cord-276617-chgjpg0v.txt
cache: ./cache/cord-276617-chgjpg0v.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s00705-008-0265-9
doi: 10.1007/s00705-008-0265-9
summary:
  The present study shows that: (1) the ratio of peripheral blood sIg(+) CD21(−) B-cells was higher in cats with FIP than in SPF cats, (2) the albumin-to-globulin ratio has negative correlation with the ratio of peripheral blood sIg(+) CD21(−) B-cell, (3) cells strongly expressing mRNA of the plasma cell master gene, B-lymphocyte-induced maturation protein 1 (Blimp-1), were increased in peripheral blood in cats with FIP, (4) mRNA expression of B-cell differentiation/survival factors, IL-6, CD40 ligand, and B-cell-activating factor belonging to the tumor necrosis factor family (BAFF), was enhanced in macrophages in cats with FIP, and (5) mRNAs of these B-cell differentiation/survival factors were overexpressed in antibody-dependent enhancement (ADE)-induced macrophages. We also collected macrophages from FIP cats and measured the expression levels of the viral RNA and mRNA of B-cell differentiation/survival factors: IL-6, CD40 ligand (CD40L), and Bcell-activating factor belonging to the tumor necrosis factor family (BAFF).

title:
  B-cell activation in cats with feline infectious peritonitis (FIP) by FIP-virus-induced B-cell differentiation/survival factors

abstract:
  It has been suggested that antibody overproduction plays a role in the pathogenesis of feline infectious peritonitis (FIP). However, only a few studies on the B-cell activation mechanism after FIP virus (FIPV) infection have been reported. The present study shows that: (1) the ratio of peripheral blood sIg(+) CD21(−) B-cells was higher in cats with FIP than in SPF cats, (2) the albumin-to-globulin ratio has negative correlation with the ratio of peripheral blood sIg(+) CD21(−) B-cell, (3) cells strongly expressing mRNA of the plasma cell master gene, B-lymphocyte-induced maturation protein 1 (Blimp-1), were increased in peripheral blood in cats with FIP, (4) mRNA expression of B-cell differentiation/survival factors, IL-6, CD40 ligand, and B-cell-activating factor belonging to the tumor necrosis factor family (BAFF), was enhanced in macrophages in cats with FIP, and (5) mRNAs of these B-cell differentiation/survival factors were overexpressed in antibody-dependent enhancement (ADE)-induced macrophages. These data suggest that virus-infected macrophages overproduce B-cell differentiation/survival factors, and these factors act on B-cells and promote B-cell differentiation into plasma cells in FIPV-infected cats.


id: cord-280621-tph5n7ak
author: Kim, Yunjeong
date: 2016-03-30
txt: ./txt/cord-280621-tph5n7ak.txt
cache: ./cache/cord-280621-tph5n7ak.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27027316/
doi: 10.1371/journal.ppat.1005531
summary:
  Shifts in tissue or cell tropism and resulting changes in virulence have also been reported for coronaviruses; porcine respiratory coronavirus causes mild respiratory infection in pigs and presumably arose from transmissible gastroenteritis virus (TGEV), the etiologic agent of gastroenteritis in young pigs with a high fatality, by spontaneous mutations and/or deletions in its genome [9] . Effective treatment intervention for coronavirus infections with an immunopathological component, such as SARS, MERS and FIP, is speculated to involve the judicious use of immunomodulatory agents to enhance protective host immunity and decrease pathological immune responses and antiviral drugs to directly inhibit viral replication. These results on viral titers show that FIPV 3CLpro is a valid target for FIPV antiviral drugs and GC376 can effectively reduce the virus load in the macrophages from the ascites and the omentum of cats with FIP.

title:
  Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor

abstract:
  Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans.


id: cord-283132-rfw8njpo
author: Olsen, Christopher W.
date: 1993-07-31
url: https://www.sciencedirect.com/science/article/pii/037811359390126R
doi: 10.1016/0378-1135(93)90126-r
title:
  A review of feline infectious peritonitis virus: molecular biology, immunopathogenesis, clinical aspects, and vaccination

abstract:
  Abstract Feline infectious peritontis (FIP) has been an elusive and frustrating problem for veterinary practitioners and cat breeders for many years. Over the last several years, reports have begun to elucidate aspects of the molecular biology of the causal virus (FIPV). These papers complement a rapidly growing base of knowledge concerning the molecular organization and replication of coronaviruses in general. The fascinating immunopathogenesis of FIPV infection and the virus' interaction with macrophages has also been the subject of several recent papers. It is now clear that FIPV may be of interest to scientists other than veterinary virologists since its pathogenesis may provide a useful model system for other viruses whose infectivity is enhanced in the presence of virus-specific antibody. With these advances and the recent release of the first commercially-available FIPV vaccine, it is appropriate to review what is known about the organization and replication of coronaviruses and the pathogenesis of FIPV infection.


id: cord-283739-p7b4mtbl
author: Theerawatanasirikul, Sirin
date: 2020-09-07
txt: ./txt/cord-283739-p7b4mtbl.txt
cache: ./cache/cord-283739-p7b4mtbl.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0166354220303417?v=s5
doi: 10.1016/j.antiviral.2020.104927
summary:
  We investigated the potential drug-liked compounds and their inhibitory interaction on the 3CL(pro) active sites of CoVs by the structural-bases virtual screening. Evaluation of antiviral activity using cell-based assay showed that NSC629301 and NSC71097 could strongly inhibit the cytopathic effect and also reduced replication of FIPV in CRFK cells in all examined conditions with the low range of EC(50) (6.11 ± 1.90 to 7.75 ± 0.48 μM and 1.99 ± 0.30 to 4.03 ± 0.60 μM, respectively), less than those of ribavirin and lopinavir. According to the FIPV 3CL pro structurral based study, we determined if the candidate 293 compounds that could bind to the active site and inhibited the protease activity still actively 294 Cys144 and His41, the active residues of FIPV 3CL pro , formed the π-alkyl interaction 352 and hydrogen bond to the compounds, respectively.

title:
  Structural-based virtual screening and in vitro assays for small molecules inhibiting the feline coronavirus 3CL protease as a surrogate platform for coronaviruses

abstract:
  Feline infectious peritonitis (FIP) which is caused by feline infectious peritonitis virus (FIPV), a variant of feline coronavirus (FCoV), is a member of family Coronaviridae, together with severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. So far, neither effective vaccines nor approved antiviral therapeutics are currently available for the treatment of FIPV infection. Both human and animal CoVs shares similar functional proteins, particularly the 3CL protease (3CL(pro)), which plays the pivotal role on viral replication. We investigated the potential drug-liked compounds and their inhibitory interaction on the 3CL(pro) active sites of CoVs by the structural-bases virtual screening. Fluorescence resonance energy transfer (FRET) assay revealed that three out of twenty-eight compounds could hamper FIPV 3CL(pro) activities with IC(50) of 3.57 ± 0.36 μM to 25.90 ± 1.40 μM, and Ki values of 2.04 ± 0.08 to 15.21 ± 1.76 μM, respectively. Evaluation of antiviral activity using cell-based assay showed that NSC629301 and NSC71097 could strongly inhibit the cytopathic effect and also reduced replication of FIPV in CRFK cells in all examined conditions with the low range of EC(50) (6.11 ± 1.90 to 7.75 ± 0.48 μM and 1.99 ± 0.30 to 4.03 ± 0.60 μM, respectively), less than those of ribavirin and lopinavir. Analysis of FIPV 3CL(pro)-ligand interaction demonstrated that the selected compounds reacted to the crucial residues (His41 and Cys144) of catalytic dyad. Our investigations provide a fundamental knowledge for the further development of antiviral agents and increase the number of anti-CoV agent pools for feline coronavirus and other related CoVs.


id: cord-287157-6rwevq39
author: Kiss, I.
date: 2004-02-25
txt: ./txt/cord-287157-6rwevq39.txt
cache: ./cache/cord-287157-6rwevq39.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1098612X04000051
doi: 10.1016/j.jfms.2003.08.009
summary:
  authors: Kiss, I.; Poland, A.M.; Pedersen, N.C. title: Disease outcome and cytokine responses in cats immunized with an avirulent feline infectious peritonitis virus (FIPV)-UCD1 and challenge-exposed with virulent FIPV-UCD8 Feline infectious peritonitis (FIP) is a highly fatal disease in Felidae caused by a coronavirus and usually affects cats between 6 months and 3 years of age (reviewed by Pedersen, 1995) . Three of eight vaccinated cats (nos 522, 616, 622) developed effusive FIP within 2 weeks of challengeexposure to FIPV-UCD8, typical of classical nonenhanced disease (Pedersen and Boyle, 1980) ( Table 1) . In this study, two of eight vaccinated cats (nos 524 and 625) appeared immune to challenge-exposure with virulent FIPV-UCD8 and two (nos 623 and 624) developed non-effusive FIP (indicative of partial immunity; Pedersen, 1995) . In the presented preliminary experiment, vaccination of cats with an attenuated live strain of FIPV-UCD1 appeared to induce a degree of protection, in that two of eight cats were immune and two more developed non-effusive FIP post challenge.

title:
  Disease outcome and cytokine responses in cats immunized with an avirulent feline infectious peritonitis virus (FIPV)-UCD1 and challenge-exposed with virulent FIPV-UCD8

abstract:
  Eight cats were immunized with an avirulent strain of feline infectious peritonitis virus (FIPV)-UCD1, then challenge-exposed to a highly virulent cat passaged strain (FIPV-UCD8). Th1 and Th2 cytokine profiles in the peripheral blood mononuclear cells (PBMCs) were measured throughout in the experiment. No clinical signs of FIP were evident in the experimental cats after immunization. After challenge, the immunized cats demonstrated one of four clinical outcomes: (1) classical effusive FIP; (2) accelerated FIP; (3) non-effusive FIP, or (4) resistance to challenge. Only minor cytokine changes were observed following immunization, however, several cytokine changes occurred following challenge-exposure. The most noteworthy changes were in tumor necrosis factor-alpha (TNF-α) and interferon gamma (IFN-γ) levels. Our preliminary findings suggest that immunity against FIP is associated with TNF-α and IFN-γ response imbalance, with high TNF-α/low IFN-γ mRNA responses favouring disease and low TNF-α/high IFN-γ mRNA responses being indicative of immunity.


id: cord-290540-r0d6oaez
title: The molecular dynamics of feline coronaviruses
author: Rottier, Peter J.M.
date: 1999-09-01
txt: ./txt/cord-290540-r0d6oaez.txt
cache: ./cache/cord-290540-r0d6oaez.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0378113599000991
doi: 10.1016/s0378-1135(99)00099-1
summary:
  Special attention is given to the genetic dynamics of the viruses as these now allow us to begin to understand the origin of the different phenotypes, in particular the genesis of virulence during persistent infection. The conclusion from these experiments is that feline coronaviruses may persist in the lower intestinal tract where the virus continues to replicate at low levels. Conceivably, the persisting virus confers to its host resistance against superinfection by the closely related feline coronaviruses, which were infecting the other cats. The idea was that''feline enteric coronaviruses'' are indeed restricted in tropism, while''FIP viruses'' would cross the epithelium, infect macrophages and go systemically. The result of all these studies is that generally there is no protection when an antibody response to the spike protein is induced there is rather an enhancement of the infection, with an''early death'' phenomenon. Detection of feline coronavirus RNA in feces, tissues and body fluids of naturally infected cats by reverse transcriptase PCR

abstract:
  Feline coronaviruses are widespread and come in different flavors. There are two main serotypes both of which occur in two pathotypes, the avirulent enteric viruses and the virulent, usually fatal peritonitis viruses, the latter in turn occurring either in a ‘wet’ or exudative form or in a ‘dry’ or proliferative form. In this paper a concise overview is given of the molecular features of these viruses. Special attention is given to the genetic dynamics of the viruses as these now allow us to begin to understand the origin of the different phenotypes, in particular the genesis of virulence during persistent infection. As discussed, the surprising new insights obtained over the last few years call for a critical reevaluation of strategies for protection.


id: cord-291707-dzmvjh7j
author: Tupper, G. T.
date: 1987
url: https://www.ncbi.nlm.nih.gov/pubmed/3619653/
doi: 10.1007/bf01310988
title:
  Antigenic and biological diversity of feline coronaviruses: feline infectious peritonitis and feline enteritis virus

abstract:
  Antigenically related feline coronaviruses cause two distinct disease manifestations in infected cats. The diseases are feline infectious peritonitis (FIP), in which the virus is widely disseminated, and feline enteric coronavirus (FECV), a mild disease in which the virus is usually limited to the villi. These two viruses were found to differ in their growth in cell culture. FIPV grows to higher titer, forms larger plaques and switches off host cell protein synthesis more effectively than FECV. Cross neutralization studies showed antigenic differences between the strains. There also appeared to be a difference in the nucleoprotein molecular weight of the viruses causing these two different disease syndromes.


id: cord-291858-e0s3o2r4
title: Feline Coronaviruses: Pathogenesis of Feline Infectious Peritonitis
author: Tekes, G.
date: 2016-08-31
txt: ./txt/cord-291858-e0s3o2r4.txt
cache: ./cache/cord-291858-e0s3o2r4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/bs.aivir.2016.08.002
doi: 10.1016/bs.aivir.2016.08.002
summary:
  Feline infectious peritonitis (FIP) belongs to the few animal virus diseases in which, in the course of a generally harmless persistent infection, a virus acquires a small number of mutations that fundamentally change its pathogenicity, invariably resulting in a fatal outcome. We discuss the recent progress in the development of FCoV reverse genetics systems suitable to generate recombinant field viruses containing appropriate mutations for in vivo studies. Deletions of the entire FCoV ORF 3 and 7 genome regions showed that the accessory genes are dispensable for viral growth in vitro; they were suggested to be important for virus replication and virulence in vivo (Haijema et al., 2004) . According to pathogenicity, FCoVs are separated into two biotypes that are generally referred to as feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). Molecular characterization of feline infectious peritonitis virus strain DF-2 and studies of the role of ORF3abc in viral cell tropism

abstract:
  Feline infectious peritonitis (FIP) belongs to the few animal virus diseases in which, in the course of a generally harmless persistent infection, a virus acquires a small number of mutations that fundamentally change its pathogenicity, invariably resulting in a fatal outcome. The causative agent of this deadly disease, feline infectious peritonitis virus (FIPV), arises from feline enteric coronavirus (FECV). The review summarizes our current knowledge of the genome and proteome of feline coronaviruses (FCoVs), focusing on the viral surface (spike) protein S and the five accessory proteins. We also review the current classification of FCoVs into distinct serotypes and biotypes, cellular receptors of FCoVs and their presumed role in viral virulence, and discuss other aspects of FIPV-induced pathogenesis. Our current knowledge of genetic differences between FECVs and FIPVs has been mainly based on comparative sequence analyses that revealed “discriminatory” mutations that are present in FIPVs but not in FECVs. Most of these mutations result in amino acid substitutions in the S protein and these may have a critical role in the switch from FECV to FIPV. In most cases, the precise roles of these mutations in the molecular pathogenesis of FIP have not been tested experimentally in the natural host, mainly due to the lack of suitable experimental tools including genetically engineered virus mutants. We discuss the recent progress in the development of FCoV reverse genetics systems suitable to generate recombinant field viruses containing appropriate mutations for in vivo studies.


id: cord-292570-618bt2vh
title: Apoptosis transcriptional mechanism of feline infectious peritonitis virus infected cells
author: Shuid, Ahmad Naqib
date: 2015-09-19
txt: ./txt/cord-292570-618bt2vh.txt
cache: ./cache/cord-292570-618bt2vh.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s10495-015-1172-7
doi: 10.1007/s10495-015-1172-7
summary:
  Based on bioinformatics analysis, five deregulated genes of the apoptosis cluster were chosen for further analysis; namely, Ras association (RalGDS/AF-6) domain family member 1 (RASSF1), Basic Leucine Zipper Transcriptional Factor ATF-Like 2 (BATF2), Melanoma antigen family B 16 (MAGEB16), Programmed cell death 5 (PDCD5) and TNF receptor-associated factor 2 (TRAF2). Although TNFa did not show significant deregulation at 9 hpi using RNA-seq analysis, the number of related affected genes including significant up regulation of FADD, TRADD, TRAF2, Tumor necrosis factor induced protein 1 and 3 (TNFAIP1 and TNFAIP3) show the importance of analysis of this cytokine during apoptosis mechanism of FIPV. After investigation of the trend of apoptosis and expression change of selected genes from apoptosis cluster, the TNF receptor-associated factor 2 (TRAF2) and programmed cell death-5 (PDCD5) were the only genes that showed significant up regulation from the first hour after infection (Fig. 3) .

abstract:
  Apoptosis has been postulated to play an important role during feline infectious peritonitis virus (FIPV) infection; however, its mechanism is not well characterized. This study is focused on apoptosis and transcriptional profiling of FIPV-infected cells following in vitro infection of CRFK cells with FIPV 79-1146 WSU. Flow cytometry was used to determine mode of cell death in first 42 h post infection (hpi). FIPV infected cells underwent early apoptosis at 9 hpi (p < 0.05) followed by late apoptosis at 12 hpi (p < 0.05) and necrosis from 24 hpi (p < 0.05). Then, next generation sequencing was performed on 9 hpi and control uninfected cells by Illumina analyzer. An aggregate of 4546 genes (2229 down-regulated and 2317 up-regulated) from 17 cellular process, 11 molecular functions and 130 possible biological pathways were affected by FIPV. 131 genes from apoptosis cluster (80 down-regulated and 51 up-regulated) along with increase of apoptosis, p53, p38 MAPK, VEGF and chemokines/cytokines signaling pathways were probably involved in apoptosis process. Six of the de-regulated genes expression (RASSF1, BATF2, MAGEB16, PDCD5, TNFα and TRAF2) and TNFα protein concentration were analyzed by RT-qPCR and ELISA, respectively, at different time-points. Up-regulations of both pro-apoptotic (i.e. PDCD5) and anti-apoptotic (i.e. TRAF2) were detected from first hpi and continuing to deregulate during apoptosis process in the infected cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10495-015-1172-7) contains supplementary material, which is available to authorized users.


id: cord-292908-rbn3foj3
author: Hohdatsu, T.
date: 1991-06-30
txt: ./txt/cord-292908-rbn3foj3.txt
cache: ./cache/cord-292908-rbn3foj3.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/037811359190096X
doi: 10.1016/0378-1135(91)90096-x
summary:
  title: Antigenic analysis of feline coronaviruses with monoclonal antibodies (MAbs): Preparation of MAbs which discriminate between FIPV strain 79-1146 and FECV strain 79-1683 Abstract We prepared 31 monoclonal antibodies (MAbs) against either FIPV strain 79-1146 or FECV strain 79-1683, and tested them for reactivity with various coronaviruses by indirect flourescent antibody assay (IFA). Sixteen MAbs which reacted with all of the 11 strains of feline coronaviruses, also reacted with canine coronavirus (CCV) and transmissible gastroenteritis virus (TGEV). For serological diagnosis of feline infectious peritonitis virus (FIPV) infection, detection of antibody by indirect fluorescent antibody assay (IFA) is popular (Pedersen, 1976b; Horzinek and Osterhaus, 1979; Scott, 1979) . They divided FIPV into Types I and II according to the presence or absence of the induction of FIP, ability of the viruses to proliferate in cell cultures, and the antigenic relationship with porcine and canine coronaviruses.

title:
  Antigenic analysis of feline coronaviruses with monoclonal antibodies (MAbs): Preparation of MAbs which discriminate between FIPV strain 79-1146 and FECV strain 79-1683

abstract:
  Abstract We prepared 31 monoclonal antibodies (MAbs) against either FIPV strain 79-1146 or FECV strain 79-1683, and tested them for reactivity with various coronaviruses by indirect flourescent antibody assay (IFA). Sixteen MAbs which reacted with all of the 11 strains of feline coronaviruses, also reacted with canine coronavirus (CCV) and transmissible gastroenteritis virus (TGEV). In many of them, the polypeptide specifity was the recognition of transmembrane (E1) protein of the virus. We succeeded in obtaining MAbs which did not react with eight strains FIPV Type I viruses (showing cell-associated growth) but reacted with FIPV Type II (79-1146, KU-1) and/or FECV Type II (79-1683) viruses (showing non-cell associated growth). These MAbs also reacted with CCV or TGEV. These MAbs recognized peplomer (E2) glycoprotein, and many antigenic differences were found in this E2 protein. These results suggest that FIPV Type II and FECV Type II viruses are antigenically closer to TGEV or CCV than to FIPV Type I viruses. Furthermore, the MAb prepared in this study has enabled discrimination between FIPV strain 79-1146 and FECV strain 79-1683, which was thought to be impossible by the previous serological method.


id: cord-293565-420thmsr
title: Spike Protein Fusion Peptide and Feline Coronavirus Virulence
author: Chang, Hui-Wen
date: 2012-07-17
txt: ./txt/cord-293565-420thmsr.txt
cache: ./cache/cord-293565-420thmsr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22709821/
doi: 10.3201/eid1807.120143
summary:
  These viruses occur as 2 pathotypes with an enigmatic, even controversial, relationship: the lowvirulence or nonvirulent feline enteric coronavirus (FECV) and the highly lethal feline infectious peritonitis virus (FIPV). To identify the distinguishing difference(s) between the FCoV pathotypes, we initiated a full genome sequencing program of FECVs found in the feces of apparently healthy cats and of FIPVs found in organs or ascites of cats with pathologically confi rmed feline infectious peritonitis. Thus, we propose that alternative mutations in the S protein of FECV give rise to a tropism change that allows the virus to escape from the intestine into body tissues, where it causes feline infectious peritonitis. Phylogenetic tree based on partial amino acid sequences (aa 1056-1069) of the spike proteins of 118 feline infectious peritonitis viruses (FIPVs) and 183 feline enteric coronaviruses (FECVs) obtained by using reverse transcription nested PCR and sequencing of the distinguishing genomic region.

abstract:
  Coronaviruses are well known for their potential to change their host or tissue tropism, resulting in unpredictable new diseases and changes in pathogenicity; severe acute respiratory syndrome and feline coronaviruses, respectively, are the most recognized examples. Feline coronaviruses occur as 2 pathotypes: nonvirulent feline enteric coronaviruses (FECVs), which replicate in intestinal epithelium cells, and lethal feline infectious peritonitis viruses (FIPVs), which replicate in macrophages. Evidence indicates that FIPV originates from FECV by mutation, but consistent distinguishing differences have not been established. We sequenced the full genome of 11 viruses of each pathotype and then focused on the single most distinctive site by additionally sequencing hundreds of viruses in that region. As a result, we identified 2 alternative amino acid differences in the putative fusion peptide of the spike protein that together distinguish FIPV from FECV in >95% of cases. By these and perhaps other mutations, the virus apparently acquires its macrophage tropism and spreads systemically.


id: cord-299342-l8ugjou9
author: Yaling, Zhou
date: 1988
txt: ./txt/cord-299342-l8ugjou9.txt
cache: ./cache/cord-299342-l8ugjou9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/3196169/
doi: 10.1007/bf01315563
summary:
  Using gut sections from pigs infected with porcine epidemic diarrhea virus (strain CV 777) and ascitic fluid from cats which had succumbed to feline infectious peritonitis (FIP), a weak cross reaction was found by immunofluorescence. No reaction was found at the nucleocapsid protein position when blots of a mock infected N L F K cell lysate had been incubated with anti-CV 777 antibodies. As shown in figure 3 , results of the RIP confirmed the cross-reaction between pig anti-CV 777 sera and the 43,000 protein of FIPV found in Western blots; the homologous reaction reveals the typical pattern of FIPV structural polypeptides with Mr of 210,000 (peplomer), 45,000 (nucleocapsid) and 25,000 to 32,000 (envelope). We have confirmed the finding of cross reactions within one group, namely between transmissible gastroenteritis virus (TGEV) of swine, FIPV and canine enteric coronavirus, and showed that common determinants are present on all three structural polypeptides [7] .

title:
  Porcine epidemic diarrhea virus (CV 777) and feline infectious peritonitis virus (FIPV) are antigenically related

abstract:
  Using gut sections from pigs infected with porcine epidemic diarrhea virus (strain CV 777) and ascitic fluid from cats which had succumbed to feline infectious peritonitis (FIP), a weak cross reaction was found by immunofluorescence. Its specificity was confirmed when detergent-treated purified CV 777 showed a prominent reaction with FIPV antibodies in ELISA; no reaction was obtained with intact virions, which indicated common determinants on an internal component of the particle. Antigenic cross-reactions at the nucleocapsid level were found in Western blot ELISA performed both ways (CV 777/FIPV antibodies; FIPV/CV 777 antibodies). In immunoprecipitation using [(35)S]methionine labelled FIPV, anti-CV 777 sera recognized exclusively the nucleocapsid protein. The significance of these findings for the classification of coronaviruses is discussed.


id: cord-299904-i5c6nf18
author: Cornelissen, E.
date: 2009-04-07
txt: ./txt/cord-299904-i5c6nf18.txt
cache: ./cache/cord-299904-i5c6nf18.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.virusres.2009.03.017
doi: 10.1016/j.virusres.2009.03.017
summary:
  authors: Cornelissen, E.; Dewerchin, H.L.; Van Hamme, E.; Nauwynck, H.J. title: Absence of antibody-dependent, complement-mediated lysis of feline infectious peritonitis virus-infected cells ADCML consists of virus-specific antibodies that bind to cell surface expressed viral proteins which result in complement activation and cell lysis. ADCML consists of virus-specific antibodies that bind to cell surface expressed viral proteins which result in complement activation and cell lysis. Surprisingly, no lysis was observed in the CrFK cells and the monocytes that do show surface-expressed viral proteins, while controls showed that the ADCML assay was functional. Surprisingly, no lysis was observed in the CrFK cells and the monocytes that do show surface-expressed viral proteins, while controls showed that the ADCML assay was functional. Absence of surface expression of feline infectious peritonitis virus (FIPV) antigens on infected cells isolated from cats with FIP Feline infectious peritonitis virus-infected monocytes internalize viral membrane-bound proteins upon antibody addition

title:
  Absence of antibody-dependent, complement-mediated lysis of feline infectious peritonitis virus-infected cells

abstract:
  Cats infected with virulent feline coronavirus which causes feline infectious peritonitis (FIP) usually succumb to disease despite high antibody concentrations. One of the mechanisms that can help resolving infection is antibody-dependent, complement-mediated lysis (ADCML) of infected cells. ADCML consists of virus-specific antibodies that bind to cell surface expressed viral proteins which result in complement activation and cell lysis. The objective of this study was to determine the sensitivity of FIP-virus (FIPV) infected cells towards ADCML and to examine the role of the accessory proteins 3abc and 7ab in this process. ADCML assays, using FIPV strain 79-1146 and its deletion mutant strain Δ3abc/Δ7ab, were performed on: (i) CrFK cells that show surface-expressed viral antigens, (ii) monocytes without surface-expressed viral proteins due to retention and (iii) monocytes with surface-expressed viral proteins since the antibody-mediated internalization of these proteins was blocked. As expected, no ADCML was detected of the monocytes without surface-expressed viral antigens. Surprisingly, no lysis was observed in the CrFK cells and the monocytes that do show surface-expressed viral proteins, while controls showed that the ADCML assay was functional. These experiments proof that FIPV can employ another immune evasion strategy against ADCML (besides preventing surface expression): the inhibition of complement-mediated lysis. This new evasion strategy is not attributed to the group-specific proteins since lysis of cells infected with FIPV Δ3abc/Δ7ab was not detected.


id: cord-299976-36r794ow
author: O’Brien, Amornrat
date: 2018-12-01
url: https://doi.org/10.1016/j.virol.2018.08.022
doi: 10.1016/j.virol.2018.08.022
title:
  Characterizing replication kinetics and plaque production of type I feline infectious peritonitis virus in three feline cell lines

abstract:
  Investigating type I feline coronaviruses (FCoVs) in tissue culture is critical for understanding the basic virology, pathogenesis, and virus-host interactome of these important veterinary pathogens. This has been a perennial challenge as type I FCoV strains do not easily adapt to cell culture. Here we characterize replication kinetics and plaque formation of a model type I strain FIPV Black in Fcwf-4 cells established at Cornell University (Fcwf-4 CU). We determined that maximum virus titers (>10(7) pfu/mL) were recoverable from infected Fcwf-4 CU cell-free supernatant at 20 hours post-infection. Type I FIPV Black and both biotypes of type II FCoV formed uniform and enumerable plaques on Fcwf-4 CU cells. Therefore, these cells were employable in a standardized plaque assay. Finally, we determined that the Fcwf-4 CU cells were morphologically distinct from feline bone marrow-derived macrophages and were less sensitive to exogenous type I interferon than were Fcwf-4 cells purchased from ATCC.


id: cord-300489-gzcb6uqw
author: Martinez, Mitzi L.
date: 1993-03-31
txt: ./txt/cord-300489-gzcb6uqw.txt
cache: ./cache/cord-300489-gzcb6uqw.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/037811359390016Z
doi: 10.1016/0378-1135(93)90016-z
summary:
  title: Detection of feline infectious peritonitis virus infection in cell cultures and peripheral blood mononuclear leukocytes of experimentally infected cats using a biotinylated cDNA probe Abstract A dot blot hybridization assay, using a biotinylated cDNA probe, was able to detect feline infectious peritonitis virus (FIPV) RNA in Felis catus whole fetus (fcwf-4) cells infected with the FIPV isolates DF2, 79-1146, UCDI, and UCD2. In an in vivo study, the probe was used to detect FIPV RNA in peripheral blood mononuclear leukocytes (PBML) isolated at various post-infection days (PID) from cats experimentally infected with the FIP-producing coronavirus isolate FIPV-79-1146 or FIPV-DF2. In this study, we describe a dot blot hybridization procedure, using a biotinylated recombinant cDNA probe complementary to a major portion of the N protein gene, to detect FIPV in feline cell cultures and PBML isolated from cats infected experimentally with the virulent FIP virus isolate 79-1146 or DF2.

title:
  Detection of feline infectious peritonitis virus infection in cell cultures and peripheral blood mononuclear leukocytes of experimentally infected cats using a biotinylated cDNA probe

abstract:
  Abstract A dot blot hybridization assay, using a biotinylated cDNA probe, was able to detect feline infectious peritonitis virus (FIPV) RNA in Felis catus whole fetus (fcwf-4) cells infected with the FIPV isolates DF2, 79-1146, UCDI, and UCD2. The probe cross-hybridized in the dot blot assay with nucleic acid of a closely related feline coronavirus, feline enteric coronavirus (FECV)-79-1683. To construct the probe, a 2.5 kilobase cDNA, prepared from FIPV-DF2 genomic RNA, was molecularly cloned. The recombinant cDNA clone was digested with the restriction endonuclease Rsa I, and an 870 basepair Rsa I fragment was isolated from vector DNA by agarose electrophoresis and glassmilk purification. This fragment was complementary to the 3′ three fourths of the nucleocapsid gene. The hybridization probe was prepared by random primed labeling in the presence of biotin-11-dUTP. Using an avidin-alkaline phosphatase conjugate and chemiluminescent substrate detection system, virus could be detected in as few as 3000 infected cells. In an in vivo study, the probe was used to detect FIPV RNA in peripheral blood mononuclear leukocytes (PBML) isolated at various post-infection days (PID) from cats experimentally infected with the FIP-producing coronavirus isolate FIPV-79-1146 or FIPV-DF2. Viral RNA could be detected in as few as 12 000 PBML isolated from cats at PID 7 and in 50 000 PBML at PID 22. There was no consistent pattern, however, between hybridization results and prognosis or severity of disease at the time of sampling. Despite some cross-hybridization with FECV RNA, this probe should be useful for diagnosis of FIP, because cats infected with FECV most likely do not become viremic.


id: cord-309205-l8vjtrjq
author: Shirato, Kazuya
date: 2018-08-15
url: https://doi.org/10.1016/j.virusres.2018.06.010
doi: 10.1016/j.virusres.2018.06.010
title:
  Differential susceptibility of macrophages to serotype II feline coronaviruses correlates with differences in the viral spike protein

abstract:
  The ability to infect and replicate in monocytes/macrophages is a critically distinguishing feature between the two feline coronavirus (FCoV) pathotypes: feline enteric coronavirus (FECV; low-virulent) and feline infectious peritonitis virus (FIPV; lethal). Previously, by comparing serotype II strains FIPV 79-1146 and FECV 79-1683 and recombinant chimeric forms thereof in cultured feline bone marrow macrophages, we mapped this difference to the C-terminal part of the viral spike (S) protein (S2). In view of the later identified diagnostic difference in this very part of the S protein of serotype I FCoV pathotypes, the present study aimed to further define the contribution of the earlier observed ten amino acids difference to the serotype II virus phenotype in macrophages. Using targeted RNA recombination as a reverse genetics system we introduced the mutations singly and in combinations into the S gene and evaluated their effects on the infection characteristics of the mutant viruses in macrophages. While some of the single mutations had a significant effect, none of them fully reverted the infection phenotype. Only by combining five specific mutations the infections mediated by the FIPV and FECV spike proteins could be fully blocked or potentiated, respectively. Hence, the differential macrophage infection phenotype is caused by the cooperative effect of five mutations, which occur in five functionally different domains of the spike fusion subunit S2. The significance of these observations will be discussed, taking into account also some questions related to the identity of the virus strains used.


id: cord-311625-d7iycdyh
author: Choong, Oi Kuan
date: 2014-02-20
url: https://www.ncbi.nlm.nih.gov/pubmed/24707494/
doi: 10.1155/2014/654712
title:
  In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication

abstract:
  Feline Infectious Peritonitis (FIP) is a severe fatal immune-augmented disease in cat population. It is caused by FIP virus (FIPV), a virulent mutant strain of Feline Enteric Coronavirus (FECV). Current treatments and prophylactics are not effective. The in vitro antiviral properties of five circular Triple-Helix Forming Oligonucleotide (TFO) RNAs (TFO1 to TFO5), which target the different regions of virulent feline coronavirus (FCoV) strain FIPV WSU 79-1146 genome, were tested in FIPV-infected Crandell-Rees Feline Kidney (CRFK) cells. RT-qPCR results showed that the circular TFO RNAs, except TFO2, inhibit FIPV replication, where the viral genome copy numbers decreased significantly by 5-fold log(10) from 10(14) in the virus-inoculated cells to 10(9) in the circular TFO RNAs-transfected cells. Furthermore, the binding of the circular TFO RNA with the targeted viral genome segment was also confirmed using electrophoretic mobility shift assay. The strength of binding kinetics between the TFO RNAs and their target regions was demonstrated by NanoITC assay. In conclusion, the circular TFOs have the potential to be further developed as antiviral agents against FIPV infection.


id: cord-311982-wkg56xeq
title: Genomic RNA sequence of feline coronavirus strain FCoV C1Je
author: Dye, Charlotte
date: 2007-06-17
txt: ./txt/cord-311982-wkg56xeq.txt
cache: ./cache/cord-311982-wkg56xeq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17363313/
doi: 10.1016/j.jfms.2006.12.002
summary:
  Comparisons of the enteric (jejunum) and non-enteric (liver) derived viral RNA sequences revealed 100% nucleotide identity, a finding that questions the well accepted ''internal mutation theory'' of FIPV pathogenicity. Comparisons of the enteric (jejunum) and non-enteric (liver) derived viral RNA sequences revealed 100% nucleotide identity, a finding that questions the well accepted ''internal mutation theory'' of FIPV pathogenicity. Furthermore, the structural and accessory gene regions of viral RNA isolated from the liver of the same cat (FCoV C1Li) were sequenced and the data derived from the enteric (jejunum) and non-enteric (liver) sources were compared. Sequence data previously generated for the laboratory strain FCoV, FIPV 79-1146, were used to design primers for conventional reverse transcriptase polymerase chain reaction (RT-PCR) amplification of short lengths (100e500 bases) of the field strain RNA. Analysis of the accessory gene 7 region of the FCoV C1Je genome identifies two ORFs, which have translation products sharing high amino acid identity with proteins 7a and 7b of FIPV 79-1146.

abstract:
  This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV). Viral RNA was isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP). A consensus sequence of the jejunum-derived genomic RNA (FCoV C1Je) was determined from overlapping cDNA fragments produced by reverse transcriptase polymerase chain reaction (RT-PCR) amplification. RT-PCR products were sequenced by a reiterative sequencing strategy and the genomic RNA termini were determined using a rapid amplification of cDNA ends PCR strategy. The FCoV C1Je genome was found to be 29,255 nucleotides in length, excluding the poly(A) tail. Comparison of the FCoV C1Je genomic RNA sequence with that of the laboratory strain FCoV FIP virus (FIPV) 79-1146 showed that both viruses have a similar genome organisation and predictions made for the open reading frames and cis-acting elements of the FIPV 79-1146 genome hold true for FCoV C1Je. In addition, the sequence of the 3′-proximal third of the liver derived genomic RNA (FCoV C1Li), which encompasses the structural and accessory protein genes of the virus, was also determined. Comparisons of the enteric (jejunum) and non-enteric (liver) derived viral RNA sequences revealed 100% nucleotide identity, a finding that questions the well accepted ‘internal mutation theory’ of FIPV pathogenicity.


id: cord-312006-c08u4t16
title: An update on feline infectious peritonitis: Virology and immunopathogenesis
author: Pedersen, Niels C.
date: 2014-05-01
url: https://api.elsevier.com/content/article/pii/S1090023314001786
doi: 10.1016/j.tvjl.2014.04.017
abstract:
  Feline infectious peritonitis (FIP) continues to be one of the most researched infectious diseases of cats. The relatively high mortality of FIP, especially for younger cats from catteries and shelters, should be reason enough to stimulate such intense interest. However, it is the complexity of the disease and the grudging manner in which it yields its secrets that most fascinate researchers. Feline leukemia virus infection was conquered in less than two decades and the mysteries of feline immunodeficiency virus were largely unraveled in several years. After a half century, FIP remains one of the last important infections of cats for which we have no single diagnostic test, no vaccine and no definitive explanations for how virus and host interact to cause disease. How can a ubiquitous and largely non-pathogenic enteric coronavirus transform into a highly lethal pathogen? What are the interactions between host and virus that determine both disease form (wet or dry) and outcome (death or resistance)? Why is it so difficult, and perhaps impossible, to develop a vaccine for FIP? What role do genetics play in disease susceptibility? This review will explore research conducted over the last 5 years that attempts to answer these and other questions. Although much has been learned about FIP in the last 5 years, the ultimate answers remain for yet more studies.


id: cord-312247-cza4qsv5
title: Targeting non-human coronaviruses to human cancer cells using a bispecific single-chain antibody
author: Würdinger, T
date: 2005-04-21
txt: ./txt/cord-312247-cza4qsv5.txt
cache: ./cache/cord-312247-cza4qsv5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15843808/
doi: 10.1038/sj.gt.3302535
summary:
  Next, we investigated whether FIPV and fMHV could be targeted to human cancer cells by constructing a bispecific single-chain antibody directed on the one hand against the feline coronavirus spike protein – responsible for receptor binding and subsequent cell entry through virus–cell membrane fusion – and on the other hand against the human epidermal growth factor receptor (EGFR). To investigate whether scFv 23F-425 could serve as an adapter molecule for FIPV and fMHV infection via human EGFR, cultures of human cancer cell lines of different tissue origin with confirmed expression of EGFR ( Figure 4 ) were inoculated with similar amounts of FIPV or fMHV in the presence or absence of the bispecific antibody. Inoculation of Targeting non-human coronaviruses to human cancer cells T Würdinger et al FIPV and fMHV onto a number of different EGFRexpressing human cancer cell lines of various tissue origins in the presence of scFv 23F-425 resulted in infection, replication, and subsequent formation of syncytia.

abstract:
  To explore the potential of using non-human coronaviruses for cancer therapy, we first established their ability to kill human tumor cells. We found that the feline infectious peritonitis virus (FIPV) and a felinized murine hepatitis virus (fMHV), both normally incapable of infecting human cells, could rapidly and effectively kill human cancer cells artificially expressing the feline coronavirus receptor aminopeptidase N. Also 3-D multilayer tumor spheroids established from such cells were effectively eradicated. Next, we investigated whether FIPV and fMHV could be targeted to human cancer cells by constructing a bispecific single-chain antibody directed on the one hand against the feline coronavirus spike protein – responsible for receptor binding and subsequent cell entry through virus–cell membrane fusion – and on the other hand against the human epidermal growth factor receptor (EGFR). The targeting antibody mediated specific infection of EGFR-expressing human cancer cells by both coronaviruses. Furthermore, in the presence of the targeting antibody, infected cancer cells formed syncytia typical of productive coronavirus infection. By their potent cytotoxicity, the selective targeting of non-human coronaviruses to human cancer cells provides a rationale for further investigations into the use of these viruses as anticancer agents.


id: cord-322629-kv83ekg0
author: TAKANO, Tomomi
date: 2019-04-23
txt: ./txt/cord-322629-kv83ekg0.txt
cache: ./cache/cord-322629-kv83ekg0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31019150/
doi: 10.1292/jvms.18-0702
summary:
  title: Pathogenesis of oral type I feline infectious peritonitis virus (FIPV) infection: Antibody-dependent enhancement infection of cats with type I FIPV via the oral route Feline infectious peritonitis virus (FIPV) causes a severe, immune-mediated disease called FIP in domestic and wild cats. In this study, when cats passively immunized with anti-FIPV-I KU-2 antibodies were orally inoculated with FIPV-I KU-2, FIP was caused at a 50% probability, i.e., FIPV not causing FIP through oral infection caused FIP by inducing antibody-dependent enhancement. Based on the findings of this study, type I FIPV which orally infected cats may cause FIP depending on the condition. In this study, we investigated whether oral inoculation with FIPV-I KU-2 causes FIP in cats passively immunized with anti-FIPV-I KU-2 antibodies. Mutation of neutralizing/antibody-dependent enhancing epitope on spike protein and 7b gene of feline infectious peritonitis virus: influences of viral replication in monocytes/macrophages and virulence in cats

title:
  Pathogenesis of oral type I feline infectious peritonitis virus (FIPV) infection: Antibody-dependent enhancement infection of cats with type I FIPV via the oral route

abstract:
  Feline infectious peritonitis virus (FIPV) causes a severe, immune-mediated disease called FIP in domestic and wild cats. It is unclear whether FIP transmits from cat to cat through the oral route of FIPV infection, and the reason for this includes that FIP is caused by oral inoculation with some FIPV strains (e.g., type II FIPV WSU 79-1146), but is not caused by other FIPV (e.g., type I FIPV KU-2 strain: FIPV-I KU-2). In this study, when cats passively immunized with anti-FIPV-I KU-2 antibodies were orally inoculated with FIPV-I KU-2, FIP was caused at a 50% probability, i.e., FIPV not causing FIP through oral infection caused FIP by inducing antibody-dependent enhancement. Many strains of type I FIPV do not cause FIP by inoculation through the oral route in cats. Based on the findings of this study, type I FIPV which orally infected cats may cause FIP depending on the condition.


id: cord-323805-9n63ms3c
author: Pedersen, Niels C.
date: 2014-11-15
txt: ./txt/cord-323805-9n63ms3c.txt
cache: ./cache/cord-323805-9n63ms3c.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.vetimm.2014.09.001
doi: 10.1016/j.vetimm.2014.09.001
summary:
  The cats were from several studies conducted over the past 5 years, and as a result, some of them had prior exposure to feline enteric coronavirus (FECV) or avirulent FIPVs. The cats were housed under optimized conditions of nutrition, husbandry, and quarantine to eliminate most of the cofactors implicated in FIPV infection outcome and were uniformly challenge exposed to the same field strain of serotype 1 FIPV. The cats were from several studies conducted over the past 5 years, and as a result, some of them had prior exposure to feline enteric coronavirus (FECV) or avirulent FIPVs. The cats were housed under optimized conditions of nutrition, husbandry, and quarantine to eliminate most of the cofactors implicated in FIPV infection outcome and were uniformly challenge exposed to the same field strain of serotype 1 FIPV. Genome-wide association studies (GWAS) on 73 cats that died of FIP after one or more exposures (cases) and 34 cats that survived (controls) demonstrated four significant associations after 100k permutations.

title:
  The influence of age and genetics on natural resistance to experimentally induced feline infectious peritonitis

abstract:
  Naturally occurring feline infectious peritonitis (FIP) is usually fatal, giving the impression that immunity to the FIP virus (FIPV) is extremely poor. This impression may be incorrect, because not all cats experimentally exposed to FIPV develop FIP. There is also a belief that the incidence of FIP may be affected by a number of host, virus, and environmental cofactors. However, the contribution of these cofactors to immunity and disease incidence has not been determined. The present study followed 111 random-bred specific pathogen free (SPF) cats that were obtained from a single research breeding colony and experimentally infected with FIPV. The cats were from several studies conducted over the past 5 years, and as a result, some of them had prior exposure to feline enteric coronavirus (FECV) or avirulent FIPVs. The cats were housed under optimized conditions of nutrition, husbandry, and quarantine to eliminate most of the cofactors implicated in FIPV infection outcome and were uniformly challenge exposed to the same field strain of serotype 1 FIPV. Forty of the 111 (36%) cats survived their initial challenge exposure to a Type I cat-passaged field strains of FIPV. Six of these 40 survivors succumbed to FIP to a second or third challenge exposure, suggesting that immunity was not always sustained. Exposure to non-FIP-inducing feline coronaviruses prior to challenge with virulent FIPV did not significantly affect FIP incidence but did accelerate the disease course in some cats. There were no significant differences in FIP incidence between males and females, but resistance increased significantly between 6 months and 1 or more years of age. Genetic testing was done on 107 of the 111 infected cats. Multidimensional scaling (MDS) segregated the 107 cats into three distinct families based primarily on a common sire(s), and resistant and susceptible cats were equally distributed within each family. Genome-wide association studies (GWAS) on 73 cats that died of FIP after one or more exposures (cases) and 34 cats that survived (controls) demonstrated four significant associations after 100k permutations. When these same cats were analyzed using a sib-pair transmission test, three of the four associations were confirmed although not with genome-wide significance. GWAS was then done on three different age groups of cases to take into account age-related resistance, and different associations were observed. The only common and strong association identified between the various GWAS case configurations was for the 34.7–45.8 Mb region of chromosome A3. No obvious candidate genes were present in this region.


id: cord-325827-492xi3ee
author: Evermann, J. F.
date: 1988
url: https://www.ncbi.nlm.nih.gov/pubmed/2849387/
doi: 10.1007/bf01310822
title:
  Biological and pathological consequences of feline infectious peritonitis virus infection in the cheetah

abstract:
  An epizootic of feline infectious peritonitis in a captive cheetah population during 1982–1983 served to focus attention on the susceptibility of the cheetah (Acinoyx jubatus) to infectious disease. Subsequent observations based upon seroepidemiological surveys and electron microscopy of fecal material verified that cheetahs were indeed capable of being infected by coronaviruses, which were antigenically related to coronaviruses affecting domestic cats, i.e. feline infectious peritonitis virus/feline enteric coronavirus. Coincident with the apparent increased susceptibility of the cheetah to infectious diseases, were observations that the cheetah was genetically unusual insofar as large amounts of enzyme-encoding loci were monomorphic, and that unrelated cheetahs were capable of accepting allogenic skin grafts. These data provided the basis for a hypothesis that the cheetah, through intensive inbreeding, had become more susceptible to viral infections as a result of genetic homogeneity.


id: cord-329642-5t8yuq4v
title: Effect of chloroquine on feline infectious peritonitis virus infection in vitro and in vivo
author: Takano, Tomomi
date: 2013-05-03
txt: ./txt/cord-329642-5t8yuq4v.txt
cache: ./cache/cord-329642-5t8yuq4v.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/23648708/
doi: 10.1016/j.antiviral.2013.04.016
summary:
  Several agents that significantly inhibit FCoV replication in vitro have been identified (Balzarini et al., 2006; Barlough and Shacklett, 1994; Hsieh et al., 2010; Kim et al., 2012; Takano et al., 2008) ; however, whether or not these agents exhibit a therapeutic effect in cats with FIP has not been investigated. The effect of chloroquine on FIPV infection in fcwf-4 cells and SPF cat-derived monocytes was investigated. In monocytes inoculated with a mixture of FIPV and MAb 6-4-2, IL-1b, TNF-a and IL-6 mRNA expression levels were significantly lower in the Pre/Post treatment group than in the None group (Fig. 3B) . The influence of chloroquine on cytokine mRNA and FCoV N gene expressions was investigated in monocytes from cats with FIP. IL-1b, TNF-a, and IL-6 mRNA expression levels of PBMC in FIPV-infected cats treated with chloroquine. In this study, chloroquine significantly inhibited inflammatory cytokine mRNA expression levels in FIPV-infected monocytes.

abstract:
  Feline infectious peritonitis (FIP) is a feline coronavirus-induced fatal disease in domestic and wild cats. Several studies have investigated potential treatments for FIP. However, there have been no reports on agents that have exhibited a therapeutic effect. Recently, chloroquine has been reported to antiviral effect. We investigated whether chloroquine can be used to treat FIP in vitro and in vivo. It was demonstrated that chloroquine has inhibitory effect against the replication of FIPV and anti-inflammatory effect in vitro. In vivo study using cats with experimentally induced FIP, the clinical score of chloroquine-treatment groups were better than in chloroquine-untreated group. However, alanine aminotransferase levels increased in the chloroquine-treated groups. It will be necessary to further investigate the possibility of FIP treatment with a combination of chloroquine and other agents.


id: cord-330554-xg49foch
title: Suppression of feline coronavirus replication in vitro by cyclosporin A
author: Tanaka, Yoshikazu
date: 2012-04-30
txt: ./txt/cord-330554-xg49foch.txt
cache: ./cache/cord-330554-xg49foch.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/1297-9716-43-41
doi: 10.1186/1297-9716-43-41
summary:
  Cyclosporin A (CsA), an immunosuppressive agent that targets the nuclear factor pathway of activated T-cells (NF-AT) to bind cellular cyclophilins (CyP), dose-dependently inhibited FIPV replication in vitro. Cyclophilin B (CyPB) is another target of CsA that promotes hepatitis C virus (HCV) replication by regulating the RNA-binding ability of the HCV NS5B protein. Here, we show that CsA inhibits intracellular replication of the FIPV genome and viral protein expression in vitro independently of the NF-AT pathway. After adsorption for 1 h at 37°C, the medium containing the virus was removed, and the cells were rinsed three times with phosphate-buffered saline [PBS (−)] and incubated with or without various concentrations of CsA (Sigma-Aldrich), cyclosporin H (CsH; Cosmobio, Tokyo, Japan) and FK506 (Sigma-Aldrich) for 20 h. Quantitative RT-PCR showed that 0.63 -10 μM CsA dose-dependently suppressed FIPV RNA replication, whereas FK506 did not exert significant inhibitory effects, except at 10 μM FK506 (approximately 30 % reduction compared to 0 μM FK506, P < 0.05; Figure 3A ).

abstract:
  The feline infectious peritonitis virus (FIPV) is a member of the feline coronavirus family that causes FIP, which is incurable and fatal in cats. Cyclosporin A (CsA), an immunosuppressive agent that targets the nuclear factor pathway of activated T-cells (NF-AT) to bind cellular cyclophilins (CyP), dose-dependently inhibited FIPV replication in vitro. FK506 (an immunosuppressor of the pathway that binds cellular FK506-binding protein (FKBP) but not CyP) did not affect FIPV replication. Neither cell growth nor viability changed in the presence of either CsA or FK506, and these factors did not affect the NF-AT pathway in fcwf-4 cells. Therefore, CsA does not seem to exert inhibitory effects via the NF-AT pathway. In conclusion, CsA inhibited FIPV replication in vitro and further studies are needed to verify the practical value of CsA as an anti-FIPV treatment in vivo.


id: cord-333403-imx3990a
title: Characterization of a temperature sensitive feline infectious peritonitis coronavirus
author: Christianson, K. K.
date: 1989
txt: ./txt/cord-333403-imx3990a.txt
cache: ./cache/cord-333403-imx3990a.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/2558634/
doi: 10.1007/bf01311080
summary:
  The characteristics of a temperature sensitive feline infectious peritonitis virus (TS-FIPV) were examined. Viral structural proteins and RNA were synthesized at 39 °C but some undefined maturational defect prevented the formation of infectious TS-FIPV at its nonpermissive temperature. TS-FIPV proteins in supernatants from cells infected at 31 °C and 39 °C were examined by Western blot. Immune sera from both TS-FIPV vaccinated cats and WT-FIPV challenged cats showed the same differences in the envelope protein of the two viruses as did the monoclonal antibody (data not shown). The culture supernatant from TS-FIPV infected cells was monitored for the appearance of structural proteins at both the permissive and nonpermissive temperatures. All three structural proteins of TS-FIPV were detected in the cells by IFA at both the permissive and nonpermissive temperatures ( Table 2 ). Surface expression of TS-FIPV and WT-FIPV peplomer and envelope proteins but not nucleocapsid at the optimal temperature for each virus resembles the situation in FIPV-infected macrophage-like cells [8] .

abstract:
  The characteristics of a temperature sensitive feline infectious peritonitis virus (TS-FIPV) were examined. TS-FIPV, unlike its parent strain, DF2 wild type FIPV (WT-FIPV), propagated at 31 °C (permissive temperature) but not at 39 °C (nonpermissive temperature). This temperature preference of TS-FIPV was also demonstrated in cats by the ability of the virus to replicate only at the lower temperature in the upper respiratory tract and not at systemic sites where higher temperatures (38–39 °C) prevail. Viral structural proteins and RNA were synthesized at 39 °C but some undefined maturational defect prevented the formation of infectious TS-FIPV at its nonpermissive temperature. TS-FIPV was more thermolabile than WT-FIPV which indicated alterations in the structural proteins of TS-FIPV, and a difference in the envelope protein of the two viruses was revealed by Western blot analysis. Plaque assay characterization showed that TS-FIPV produced small plaques in comparison to the large plaques of WT-FIPV. These unique characteristics possessed by TS-FIPV may account for its nonvirulent nature and ability to stimulate protective immune responses in cats.


id: cord-336639-jaue41mv
title: A mRNA PCR for the diagnosis of feline infectious peritonitis
author: Simons, Fermin A.
date: 2004-12-21
url: https://www.sciencedirect.com/science/article/pii/S0166093404003477
doi: 10.1016/j.jviromet.2004.11.012
abstract:
  A reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of feline coronavirus (FCoV) messenger RNA in peripheral blood mononuclear cells (PBMCs) is described. The assay is evaluated as a diagnostic test for feline infectious peritonitis (FIP). It is based on a well-documented key event in the development of FIP: the replication of virulent FCoV mutants in monocytes/macrophages. To detect most feline coronavirus field strains, the test was designed to amplify subgenomic mRNA of the highly conserved M gene. The test was applied to 1075 feline blood samples (424 from healthy, 651 from sick cats suspected of FIP) and returned 46% of the diseased cats as positive for feline coronavirus mRNA in their peripheral blood cells; of the healthy cats, 5% tested positive. Of a group of 81 animals in which FIP had been confirmed by post-mortem examination, 75 (93%) tested positive, whereas 17 cats with different pathologies (non-FIP cases) all tested negative. In view of the low rate of false-positive results (high specificity) the mRNA RT-PCR may be a valuable addition to the diagnostic arsenal for FIP.


id: cord-345863-j01l71dh
title: Host Gene Expression of Macrophages in Response to Feline Coronavirus Infection
author: Drechsler, Yvonne
date: 2020-06-09
url: https://doi.org/10.3390/cells9061431
doi: 10.3390/cells9061431
abstract:
  Feline coronavirus is a highly contagious virus potentially resulting in feline infectious peritonitis (FIP), while the pathogenesis of FIP remains not well understood, particularly in the events leading to the disease. A predominant theory is that the pathogenic FIPV arises from a mutation, so that it could replicate not only in enterocytes of the intestines but also in monocytes, subsequently systemically transporting the virus. The immune status and genetics of affected cats certainly play an important role in the pathogenesis. Considering the importance of genetics and host immune responses in viral infections, the goal of this study was to elucidate host gene expression in macrophages using RNA sequencing. Macrophages from healthy male cats infected with FIPV 79-1146 ex vivo displayed a differential host gene expression. Despite the virus uptake, aligned viral reads did not increase from 2 to 17 h. The overlap of host gene expression among macrophages from different cats was limited, even though viral transcripts were detected in the cells. Interestingly, some of the downregulated genes in all macrophages were involved in immune signaling, while some upregulated genes common for all cats were found to be inhibiting immune activation. Our results highlight individual host responses playing an important role, consistent with the fact that few cats develop feline infectious peritonitis despite a common presence of enteric FCoV.


id: cord-346321-drhiqch0
author: Hohdatsu, T.
date: 1994
url: https://www.ncbi.nlm.nih.gov/pubmed/7832635/
doi: 10.1007/bf01310791
title:
  The role of IgG subclass of mouse monoclonal antibodies in antibody-dependent enhancement of feline infectious peritonitis virus infection of feline macrophages

abstract:
  Antibody-dependent enhancement (ADE) of feline infectious peritonitis virus (FIPV) infection was studied in feline alveolar macrophages and human monocyte cell line U937 using mouse neutralizing monoclonal antibodies (MAbs) directed to the spike protein of FIPV. Even among the MAbs that have been shown to recognize the same antigenic site, IgG 2a MAbs enhanced FIPV infection strongly, whereas IgG 1 MAbs did not. These IgG 2a MAbs enhanced the infection even when macrophages pretreated with the MAb were washed and then inoculated with the virus. Immunofluorescence flow cytometric analysis of the macrophages treated with each of the MAbs showed that the IgG 2a MAbs but not the IgG 1 MAbs bound to feline alveolar macrophages. Treatment of the IgG 2a MAb with protein A decreased the binding to the macrophages and, in parallel, diminished the ADE activity. Although no infection was observed by inoculation of FIPV to human monocyte cell line U937 cells, FIPV complexed with either the IgG 2a MAb or the IgG 1 MAb caused infection in U937 cells which are shown to express Fc gamma receptor (Fc γ R) I and II that can bind mouse IgG 2a and IgG 1, respectively. These results suggest that the enhancing activity of MAb is closely correlated with IgG subclass and that the correlation is involved in binding of MAb to Fc γ R on feline macrophage.


id: cord-348204-365z3qxz
author: Harun, Mohammad Syamsul Reza
date: 2013-11-09
url: https://doi.org/10.1186/1743-422x-10-329
doi: 10.1186/1743-422x-10-329
title:
  Transcriptional profiling of feline infectious peritonitis virus infection in CRFK cells and in PBMCs from FIP diagnosed cats

abstract:
  BACKGROUND: Feline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV). Currently, the viruses virulence determinants and host gene expressions during FIPV infection are not fully understood. METHODS: RNA sequencing of Crandell Rees Feline Kidney (CRFK) cells, infected with FIPV strain 79–1146 at 3 hours post infection (h.p.i), were sequenced using the Illumina next generation sequencing approach. Bioinformatic’s analysis, based on Felis catus 2X annotated shotgun reference genome, using CLC bio Genome Workbench mapped both control and infected cell reads to 18899 genes out of 19046 annotated genes. Kal’s Z test statistical analysis was used to analyse the differentially expressed genes from the infected CRFK cells. Real time RT-qPCR was developed for further transcriptional profiling of three genes (PD-1, PD-L1 and A3H) in infected CRFK cells and Peripheral Blood Mononuclear Cells (PBMCs) from healthy and FIP-diseased cats. RESULTS: Based on Kal’s Z-test, with False Discovery Rate (FDR) <0.05 and >1.99 fold change on gene expressions, a total of 61 genes were differentially expressed by both samples, where 44 genes were up-regulated and the remainder were down-regulated. Most genes were closely clustered together, suggesting a homogeneous expression. The majority of the genes that were significantly regulated, were those associated with monocytes-macrophage and Th1 cell functions, and the regulation of apoptosis. Real time RT-qPCR developed focusing on 2 up-regulated genes (PD-L1 and A3H) together with an apoptosis associated gene PD-1 expressions in FIPV infected CRFK cells and in PBMCs from healthy and FIP diagnosed cats produced concordant results with transcriptome data. CONCLUSION: The possible roles of these genes, and their importance in feline coronaviruses infection, are discussed.


id: cord-349800-s9w2yr08
author: Hohdatsu, T.
date: 1991
txt: ./txt/cord-349800-s9w2yr08.txt
cache: ./cache/cord-349800-s9w2yr08.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/1706593/
doi: 10.1007/bf01310494
summary:
  Seven monoclonal antibodies (MAbs) with neutralizing activity against feline infectious peritonitis virus (FIPV) strain 79-1149 (type II) were prepared. The reactivity of these MAbs with 6 viruses classified as FIPV type I (UCD-1, UCD-2, UCD-3, UCD-4, NW-1, and Black), feline enteric coronavirus (FECV) type II strain 79-1683, canine coronavirus (CCV) strain 1-71, and transmissible gastroenteritis virus (TGEV) strains TO-163 and SH was examined by neutralization tests. Feline coronaviruses are divided into FIPV types I and II, and FECV types I and II, on the basis of the disease types, that is, whether it causes feline infectious peritonitis (FIP) or not, the ability of the viruses to proliferate in cell cultures, and the antigenic relationship to TGEV and CCV [17] . These MAbs did not neutralize the 6 FIPV type I viruses, but neutralized FECV strain 79-1683, TGEV strains TO-163 and SH, and CCV strain 1-71, which do not cause feline infectious peritonitis (Table 4) .

title:
  Characterization of monoclonal antibodies against feline infectious peritonitis virus type II and antigenic relationship between feline, porcine, and canine coronaviruses

abstract:
  Seven monoclonal antibodies (MAbs) with neutralizing activity against feline infectious peritonitis virus (FIPV) strain 79-1149 (type II) were prepared. When the polypeptide specificity recognized by these monoclonal antibodies (MAbs) was investigated by Western immunoblotting, all of the MAbs reacted with peplomer glycoprotein (S) of the virus. By competitive binding assay these MAbs were found to recognize at least 3 different epitopes. The reactivity of these MAbs with 6 viruses classified as FIPV type I (UCD-1, UCD-2, UCD-3, UCD-4, NW-1, and Black), feline enteric coronavirus (FECV) type II strain 79-1683, canine coronavirus (CCV) strain 1-71, and transmissible gastroenteritis virus (TGEV) strains TO-163 and SH was examined by neutralization tests. All MAbs neutralized FECV strain 79-1683, CCV strain 1-71, and TGEV strains TO-163 and SH, while they did not neutralize the 6 FIPV type I viruses. Moreover, the MAb against TGEV strain TO-163, which has strong neutralizing activity against 7 TGEV viruses, neutralized CCV strain 1-71, FECV strain 79-1683, and FIPV strain 79-1146, but did not neutralize the 6 FIPV type I viruses. These results demonstrated that there are at least 3 epitopes involved in the neutralization of FIPV type II strain 79-1146, and that these epitopes are not present in FIPV type I viruses but are present in FECV strain 79-1683 which does not induce feline infectious peritonitis, TGEV strains TO-163 and SH, and CCV strain 1-71. These results suggest the presence of 2 serotypes of FIPV which can be clearly distinguished by the neutralization test using MAbs.


id: cord-349964-38rgcc5h
title: Antigenic relationship of the feline infectious peritonitis virus to coronaviruses of other species
author: Pedersen, N. C.
date: 1978
url: https://www.ncbi.nlm.nih.gov/pubmed/81044/
doi: 10.1007/bf01315534
abstract:
  Utilizing the direct and indirect fluorescent antibody procedure, the antigenic relationship of the feline infectious peritonitis virus (FIPV) to 7 other human and animal coronaviruses was studied. FIPV was found to be closely related to transmissible gastroenteritis virus (TGEV) of swine. Transmissible gastroenteritis virus and FIPV were in turn antigenically related to human coronavirus 229E (HCV-229E) and canine coronavirus (CCV). An interesting finding in the study was that the 8 coronaviruses selected for this study fell into one of two antigenically distinct groups. Viruses in each group were antigenically related to each other to varying degrees, but were antigenically unrelated to coronaviruses of the second group. The first antigenically related group was comprised of mouse hepatitis virus, type 3 (MHV-3), hemeagglutinating encephalomyelitis virus 67N (HEV-67N) of swine, calf diarrhea coronavirus (CDCV), and human coronavirus OC43 (HCV-OC43). The second antigenically related group was comprised of FIPV, TGEV, HCV-229E and CCV.


id: cord-351955-9l4786lb
author: Pedersen, Niels C.
date: 2009-08-26
url: https://doi.org/10.3390/v1020166
doi: 10.3390/v1020166
title:
  Significance of Coronavirus Mutants in Feces and Diseased Tissues of Cats Suffering from Feline Infectious Peritonitis

abstract:
  The internal FECV→FIPV mutation theory and three of its correlates were tested in four sibs/half-sib kittens, a healthy contact cat, and in four unrelated cats that died of FIP at geographically disparate regions. Coronavirus from feces and extraintestinal FIP lesions from the same cat were always >99% related in accessory and structural gene sequences. SNPs and deletions causing a truncation of the 3c gene product were found in almost all isolates from the diseased tissues of the eight cats suffering from FIP, whereas most, but not all fecal isolates from these same cats had intact 3c genes. Other accessory and structural genes appeared normal in both fecal and lesional viruses. Deliterious mutations in the 3c gene were unique to each cat, indicating that they did not originate in one cat and were subsequently passed horizontally to the others. Compartmentalization of the parental and mutant forms was not absolute; virus of lesional type was sometimes found in feces of affected cats and virus identical to fecal type was occasionally identified in diseased tissues. Although 3c gene mutants in this study were not horizontally transmitted, the parental fecal virus was readily transmitted by contact from a cat that died of FIP to its housemate. There was a high rate of mutability in all structural and accessory genes both within and between cats, leading to minor genetic variants. More than one variant could be identified in both diseased tissues and feces of the same cat. Laboratory cats inoculated with a mixture of two closely related variants from the same FIP cat developed disease from one or the other variant, but not both. Significant genetic drift existed between isolates from geographically distinct regions of the Western US.


id: cord-355051-w18ptl0n
author: Satoh, Ryoichi
date: 2010-11-23
txt: ./txt/cord-355051-w18ptl0n.txt
cache: ./cache/cord-355051-w18ptl0n.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/21091984/
doi: 10.1111/j.1348-0421.2010.00275.x
summary:
  title: Characterization of T helper (Th)1‐ and Th2‐type immune responses caused by baculovirus‐expressed protein derived from the S2 domain of feline infectious peritonitis virus, and exploration of the Th1 and Th2 epitopes in a mouse model In FP-HR2 protein-immunized mice, the concentrations of IFN-γ and IL-2 in the supernatant of splenocytes cultured with or without FIPV antigen were significantly higher than in that of splenocytes derived from wild-type baculovirus-infected SF-9-or PBS-immunized mice (P < 0.05, P < 0.01, respectively). In IH proteinimmunized mice, the concentration of IL-2 in the supernatant of splenocytes cultured with or without FIPV antigen was significantly higher than in that of splenocytes derived from wild-type baculovirus-infected SF-9or PBS-immunized mice (P < 0.05, P < 0.01, respectively). However, in PC protein-immunized mice, the concentrations of IFN-γ and IL-2 in the supernatant of splenocytes cultured with or without FIPV antigen were not significantly higher than in that of splenocytes derived from wild-type baculovirus-infected SF-9-or PBS-immunized mice.

title:
  Characterization of T helper (Th)1‐ and Th2‐type immune responses caused by baculovirus‐expressed protein derived from the S2 domain of feline infectious peritonitis virus, and exploration of the Th1 and Th2 epitopes in a mouse model

abstract:
  Feline infectious peritonitis virus (FIPV) may cause a lethal infection in cats. Antibody‐dependent enhancement (ADE) of FIPV infection has been recognized, and cellular immunity is considered to play an important role in preventing the onset of feline infectious peritonitis. In the present study, whether or not the T helper (Th)1 epitope was present in the spike (S)2 domain was investigated, the ADE epitope being thought to be absent from this domain. Three kinds of protein derived from the C‐terminal S2 domain of S protein of the FIPV KU‐2 strain were developed using a baculovirus expression system. These expressed proteins were the pre‐coil region which is the N‐terminal side of the putative fusion protein (FP), the region from FP to the heptad repeat (HR)2 (FP‐HR2) region, and the inter‐helical region which is sandwiched between HR1 and HR2. The ability of three baculovirus‐expressed proteins to induce Th1‐ and Th2‐type immune responses was investigated in a mouse model. It was shown that FP‐HR2 protein induced marked Th1‐ and Th2‐type immune responses. Furthermore, 30 peptides derived from the FP‐HR2 region were synthesized. Five and 16 peptides which included the Th1 and Th2 epitopes, respectively, were identified. Of these, four peptides which included both Th1 and Th2 epitopes were identified. These findings suggest that the identification of Th1 epitopes in the S2 domain of FIPV has important implications in the cat.


id: cord-356112-c32icxir
author: Weiss, R. C.
date: 1988
txt: ./txt/cord-356112-c32icxir.txt
cache: ./cache/cord-356112-c32icxir.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/2848354/
doi: 10.1007/bf00343250
summary:
  Specific-pathogen-free kittens experimentally infected with feline infectious peritonitis virus (FIPV) subsequently demonstrated increased plasma levels of the arachidonic acid metabolites, leukotriene (LT) B4 and prostaglandin (PG) E2. Loss of fluid and other plasma constituents from inflamed blood vessels, immunologically damaged by complexes of virus, antiviral antibodies and complement (C) proteins (August, 1984; Barlough &Weiss, 1983; Pedersen & Boyle, 1980; Weiss & Scott, 1981~; Jacobse-Geels et al., 1982) or by cytotoxic lymphokines or other enzymatically-active factors released during cellular immune responses (Pedersen, 1985) , may occur in cases of acute FIP. Although vascular lesions, and possibly the pathologic effusions, in FIP are believed to occur via immunological (antibody-mediated) mechanisms (Pedersen, 1985; August, 1984; Weiss & Scott, 1981b; 1981c) , the occurrence of fever and increased plasma levels of LTB4 and PGE2 prior to detectable antibody responses in some FIPV-infected kittens suggest that nonimmunological factors can be involved in some disease manifestations.

title:
  Increased plasma levels of leukotriene B4 and prostaglandin E2 in cats experimentally inoculated with feline infectious peritonitis virus

abstract:
  Specific-pathogen-free kittens experimentally infected with feline infectious peritonitis virus (FIPV) subsequently demonstrated increased plasma levels of the arachidonic acid metabolites, leukotriene (LT) B4 and prostaglandin (PG) E2. Significant increases (P<0.025) in LTB4 plasma levels occurred in all (5/5) FIPV-inoculated kittens on postchallenge-exposure days (PCD) 7 and 14 vs PCD 0. Significant increases (P<0.05) in PGE2 plasma levels occurred in 80% (4/5) of FIPV-infected kittens on PCD 7 and 14. Maximal mean plasma levels of LTB4 and PGE2 occurred on PCD 7 (502.5±45.6 pg/ml and 1108.0±247.9 pg/ml, respectively). A positive correlation was found between LTB4 plasma levels and body temperature (r=0.609, P<0.01). Mean survival time in FIPV-inoculated kittens was 19.4±3.2 days. Gross lesions, including peritoneal or pleural effusions (or both) and connective tissue edema, indicated an increased vascular permeability in the FIPV-infected kittens. Histologically, lesions were characterized by pyogranulomatous inflammation. Immunofluorescent studies of tissues from FIPV-infected kittens demonstrated foci of polymorphonuclear leukocytes and FIPV-positive macrophages oriented around dilated blood vessels. Seemingly, arachidonic acid metabolites, including LTB4 or PGE2 released from macrophages, neutrophils or other cells, may be involved in the pathogenesis of FIP vascular and inflammatory lesions and in some of the clinical disease manifestations.


