cord-000403-vzbh457k 2011 Twenty-seven nanopeptides derived from the matrix (M) protein of porcine reproductive and respiratory syndrome virus (PRRSV) were screened for their ability to elicit a recall interferon-γ (IFN-γ) response from the splenocytes of BALB/c mice following DNA vaccination and a booster vaccination with recombinant vaccinia virus rWR-PRRSV-M. We screened peptides derived from the PRRSV M protein for their ability to induce interferon (IFN)-γ in splenocytes harvested from BALB/ c mice following DNA vaccination and a booster vaccination with recombinant vaccinia virus expressing M protein. In contrast, control mice vaccinated with pVAX1-only or PBS-only did not show significant increases in M protein-specific antibody titers after the booster vaccination with rWR-PRRSV-M (P > 0.05, Additional file 5, Fig. S5 ). Specific increases in the number of cells producing IFN-γ following stimulation with the peptides "K 93 FITSRCRL" and "F 57 GYMTFVHF" was observed by day 3 after the booster vaccination with rWR-PRRSV-M (Figure 1 and 2) . cord-001134-8ljgxnhf 2013 title: Comparison of viremia of type II porcine reproductive and respiratory syndrome virus in naturally infected pigs by zip nucleic acid probe-based real-time PCR In this study, we developed a sensitive and specific zip nucleic acid probe-based real-time PCR assay to evaluate the viremia of natural PRRSV-infected pigs in Taiwan. CONCLUSIONS: ZNA probe-based real-time PCR can be a useful tool to diagnose symptomatic and asymptomatic PRRSV-infected pigs. ZNA probe-based real-time PCR amplification and the limit of detection Tenfold serial plasmid dilutions (10 1 to 10 6 copies/μl) were tested and used to construct the standard curve by plotting the logarithm of the plasmid copy number against the measured quantification cycles (Cq) values. However, this is first study to report the viral load using serum samples in asymptomatic PRRSV-infected pigs using ZNA probebased real-time PCR. Development of a onestep real-time quantitative PCR assay based on primer-probe energy transfer for the detection of porcine reproductive and respiratory syndrome virus cord-001236-cgiok0ce 2014 title: An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination Therefore, we attempted to strengthen the immunogenicity of inactivated/killed PRRSV vaccine antigens (KAg), especially in the pig respiratory system, through: 1) entrapping the KAg in biodegradable poly(lactic-co-glycolic acid) nanoparticles (NP-KAg); 2) coupling the NP-KAg with a potent mucosal adjuvant, whole cell lysate of Mycobacterium tuberculosis (M. 32 In adjuvanted NP-KAgvaccinated pigs, increased avidity of virus-specific IgA was detected in both BAL fluid (both low and high doses) and lung homogenate (only low dose) samples compared to other tested groups (Figure 2A-C) . Adjuvanted poly(lactic-co-glycolic) acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs cord-001371-wf0vonkn 2014 The real-time RT-PCR developed based on SYBR Green and TaqMan probe could be used for simultaneous detection and differentiation of HP-PRRSV and PRRSV in China, which will benefit much the PRRS control and research. In this research, the real-time RT-PCR for simultaneous detection and differentiation of HP-PRRSV and PRRSV by using both SYBR Green and TaqMan probe was developed and validated. Our results showed that real-time PCR using both SYBR Green I and TaqMan probe could be used to simultaneously detect and differentiate HP-PRRSV and PRRSV in China. The real-time PCR developed based on SYBR Green and TaqMan probe could be used for simultaneous detection and differentiation of HP-PRRSV and PRRSV in China, which provided two alternative diagnostic assays in diverse PRRSV epidemiological circumstances. Simultaneous detection and genotyping of porcine reproductive and respiratory syndrome virus (PRRSV) by real-time RT-PCR and amplicon melting curve analysis using SYBR Green cord-002087-o8kffjw0 2016 title: Nonstructural protein 11 (nsp11) of porcine reproductive and respiratory syndrome virus (PRRSV) promotes PRRSV infection in MARC-145 cells RESULTS: Here, we firstly explored the effect of over-expression of nsp11 on PRRSV infection and found that over-expression of nsp11 enhanced the PRRSV titers while the small interfering RNA (siRNAs) specifically targeting nsp11 could reduce the PRRSV titers in MARC-145 cells. Abbreviations EAV, equine arteritis virus; GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; GFP-nsp11, pcDNA 3.1-GFP-nsp11; MHV, mouse hepatitis virus; MOI, multiplicity of infection; NLRP3, NLR family pyrin domain-containing 3; nsp11, nonstructural protein 11; ORF, open reading frame; PRRSV, porcine reproductive and respiratory syndrome virus ; PVDF, polyvinylidene difluoride; qRT-PCR, quantitative real-time RT-PCR; RNAi, RNA interference; siRNA, small interfering RNA; TCID50, 50 % tissue culture infected dose Identification of two auto-cleavage products of nonstructural protein 1 (nsp1) in porcine reproductive and respiratory syndrome virus infected cells: nsp1 function as interferon antagonist cord-002589-xq3iq8ai 2017 To follow up these studies, we report here on (1) the investigation of PRRSV active infection (RNA in tonsil) using the same 2013 abattoir survey sample-set and (2) an analysis of the correlation of PRRSV and HEV infection in these pigs, which could be of significance for the control of both diseases and in informing farming practices for reducing HEV in the food chain. The phylogenetic trees (Figure 1 ) illustrate the genetic diversity of the ORF5 genes from the 23 samples in this study in comparison to the vaccine virus licensed in the UK at the time and 48 published reference sequences representing the different genotypes and subtypes ( Figure 1A ) and in more detail, in the context of 431 previously sequenced viruses specifically from UK pigs between 1991 and 2014 (unpublished data) ( Figure 1B ). cord-002590-24o2viv3 2017 cord-003144-nqkw5v3w 2017 title: Label‐Free Quantitative Proteomic Analysis of Differentially Expressed Membrane Proteins of Pulmonary Alveolar Macrophages Infected with Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Its Attenuated Strain Significant differences exist between the highly pathogenic (HP) porcine reproductive and respiratory syndrome virus (PRRSV) and its attenuated pathogenic (AP) strain in the ability to infect host cells. This is the first attempt to explore the differential characteristics between HP‐PRRSV and its attenuated PRRSV infected PAMs focusing on membrane proteins which will be of great help to further understand the different infective mechanisms of HP‐PRRSV and AP‐PRRSV. Differentially expressed proteins between control and HP-PRRSV-infected cells (Con/HP) and the www.advancedsciencenews.com www.proteomics-journal.com p <0.01 and ratio >2 or <0.5 indicated quantitative difference between two groups. By analyzing detected proteins in HP-infected, AP-PRRSV-infected, and control group, proteins related to the immune response or virus replication were identified that may elucidate unique pathways used by different virulent PRRSVs for cell entry, virus replication, and immune escape mechanisms. cord-003492-rodqdtfj 2019 PRRSV is a complex disease and several gaps in the knowledge of its economic impact, biology and evolution, genetic polymorphism, mechanism of viral infections, elicitation of protective immune responses and novel control strategies, have been reviewed here (Box 1). Nonstructural proteins nsp2TF and nsp2N of porcine reproductive and respiratory syndrome virus (PRRSV) play important roles in suppressing host innate immune responses Immune responses in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) Immunodominant epitopes in nsp2 of porcine reproductive and respiratory syndrome virus are dispensable for replication, but play an important role in modulation of the host immune response Nonstructural protein 11 (nsp11) of porcine reproductive and respiratory syndrome virus (PRRSV) promotes PRRSV infection in MARC-145 cells Immune response to ORF5a protein immunization is not protective against porcine reproductive and respiratory syndrome virus infection cord-003841-7uaj9hmx 2019 The findings indicate that tulathromycin, in the absence of a direct anti-viral effect, is able to restore the phagocytic function and to attenuate the pro-inflammatory phenotype of PRRSV-infected monocyte-derived porcine macrophages. However, Immuno-modulating properties of Tulathromycin in PRRSV-infected porcine monocyte-derived macrophages PRRSV-induced IL-10 inhibition was abolished when the cells were pre-treated with tulathromycin at 2 and 12 hours post infection (Fig 6) . Another set of experiments assessed the effects of PRRSV, and of tulathromycin, on the nonopsonized and opsonized phagocytic functions of MDMs. PRRSV infection significantly Immuno-modulating properties of Tulathromycin in PRRSV-infected porcine monocyte-derived macrophages inhibited both phagocytic functions of the cells (Figs 10 and 11 ). The findings indicate that TUL inhibits PRRSV-induced inflammatory responses in porcine monocyte-derived macrophages and protects against the phagocytic impairment caused by the virus, in the absence of any direct anti-viral effects. cord-003962-lg6gvgwt 2019 cord-003970-3e58229u 2019 cord-004151-9815ikzg 2020 To investigate CTL epitope applications in swine, SLA-1(*)1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments. Next, the potential SLA-1(*)1502-restricted peptide epitopes matching four typical genetic PRRSV strains were identified based on the peptide-binding motif of SLA-1(*)1502 determined by structural analysis and alanine scanning of the NSP9-TMP9 peptide. In an attempt to identify anti-PRRSV CTL epitopes in this study, first, predicted peptide epitopes derived from PRRSV were synthesized, and a trimolecular complex, the structure of the epitope from PRRSV-NSP9 (TMPPGFELY, termed NSP9-TMP9)-bound SLA-1 * 1502 (pSLA-1 * 1502), was solved. The purified complex (44 kDa) of pSLA-1 * 1502 with the NSP9-TMP9 peptide (amino acid sequence TMPPGFELY, derived from residues 198-206 of the PRRSV non-structural protein) was dialyzed against crystallization buffer (20 mM Tris-HCl pH 8.0, 50 mM NaCl) and concentrated to 12 mg/mL. cord-004477-qu2o2iu1 2020 Immediately following viral infection, neonatal survival depends on innate immunity and passive protection by lactogenic immune factors such as pathogen-specific antibodies, until an adaptive immune response can develop. Wide-spread porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV) represent major health challenges in the large US swine production systems and possibly worldwide. In introducing the topic of anti-viral immunity, we emphasize the genetic diversity of viruses, the virus life cycle and the pathology that viral infection can cause. A more tedious procedure is to use only parts of the virus as the vaccine (subunit vaccines) that target the immune response to those viral epitopes that elicit VN antibodies. A second approach to vaccine development is use of live attenuated virus that has been genetically modified or cell culture adapted and cannot produce a disease in the host but can still replicate. cord-004754-5596p4ma 2014 cord-004838-cdas57cx 1995 title: Sequence analysis of open reading frames (ORFs) 2 to 4 of a U.S. isolate of porcine reproductive and respiratory syndrome virus The sequence of ORFs 2 to 4 of a U.S. isolate of porcine reproductive and respiratory syndrome virus (PRRSV), ATCC VR2385, was determined by analysis of a cDNA λ library. No overlap was found between ORFs 4 and 5, and instead there was a 10 bp sequence which separated these two ORFs. The nucleic acid homology with corresponding ORFs of the European PRRSV isolate Lelystad virus (LV) was 65% for ORF 2, 64% for ORF 3 and 66% for ORF 4. Cloning, expression, and sequence analysis of the ORF 4 gene of porcine reproductive and respiratory syndrome virus MN-lb Molecular cloning and nucleotide sequencing of the 3''-terminal genomic RNA of porcine reproductive and respiratory syndrome virus cord-005372-7x8ro8p2 2014 PRDC is caused by a combination of viral and bacterial agents, such as porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), Mycoplasma hyopneumoniae (Myh), Actinobacillus pleuropneumoniae (APP), Pasteurella multocida and Porcine circovirus 2 (PCV2). Our findings indicate that positive farms have increased risk of PRDC presentation, in particular, PCV2, APP and Myh. Swine infl uenza is an acute, highly contagious respiratory disease resulting from infection with type A infl uenza virus, a member of the Orthomyxoviridae family. PRDC results from a combination of viral and bacterial agents, including porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), Mycoplasma hyopneumoniae (Myh), Actinobacillus pleuropneumoniae (APP), Pasteurella multocida and porcine circovirus type 2 (PCV2) (Kim J, et al., 2003) . The main goal of the current research was to generate surveillance, epidemiological, antigenic as well as phylogenetic data to ascertain the presence of swine influenza (H1N1) pandemic virus and determine its association with PRDC (PRRSV, Myh, APP and PCV2) in sows from production farms in Colombia. cord-005376-tzmettky 2014 The K418 chimeric virus of porcine reproductive and respiratory syndrome virus (PRRSV) was engineered by replacing the genomic region containing structure protein genes of an infectious clone of PRRSV, FL12, with the same region obtained from a Korean dominant field strain, LMY. In previous studies, diverse chimera viruses of PRRSV have been generated using RG technology to manipulate viral genomes to determine the viral protein involved in the pathogenicity of field strains in pigs (Kwon et al., 2006; Zhou et al., 2012; Ni et al., 2013) . In this study, a chimeric virus was constructed using an infectious clone of PRRSV containing genomes of the FL12 strain and a Korean dominant field strain, LMY. To generate customized vaccine candidate, the genomic region of established PRRSV infectious clone encoding structure proteins that play a critical role in the virus neutralizing response were replaced with the same genomic region from a Korean dominant field strain of PRRSV. cord-005378-u2bbgn8k 2013 cord-007476-wu9tuvy9 2000 title: Antigenic differences between European and American isolates of porcine reproductive and respiratory syndrome virus (PRRSV) are encoded by the carboxyterminal portion of viral open reading frame 3 Antigenic differences between European and American isolates of porcine reproductive and respiratory syndrome virus (PRRSV) were revealed by serologic analysis of a recombinant protein derived from PRRSV open reading frame 3 (ORF 3). Sera from rabbits inoculated with BP03-P failed to neutralize both the European (Lelystad) and American (ATCC VR-2332) reference isolates of PRRSV and did not react by IPMA with PRRSV-infected cell cultures. Sera from rabbits inoculated with BPO3-P failed to neutralize both the European (Lelystad) and American ( ATCC VR-2332) reference isolates of PRRSV and did not react by IPMA with PRRSV-infected cell cultures. Two of the rabbit antipeptide sera were reproducibly reactive by western immunoblot with a diffuse (40 to 45 kDa) band of antigen found in homogenates of MARC-145 cells infected 16 h previously with the Lelystad isolate (Fig. 4) . cord-009443-0vis4bwi 2020 Furthermore, vaccination with the GP5-Mosaic based vaccines resulted in protection against challenge with two heterologous virus strains, as demonstrated by the significantly lower viral loads in serum, tissues, porcine alveolar macrophages (PAMs), and bronchoalveolar lavage (BAL) fluids, and less severe lung lesions after challenge with either MN184C or VR2332, which have only 85% identity. In contrast, the viral loads in serum of animals receiving the GP5-Mosaic-vaccine were significantly lower than those of animals receiving the GP5-WT vaccine or those of vector-control animals at 7 and 14 DPC with MN184C (* p < 0.05) ( Figure 3B ), which was different compared to VR2332-challenged groups. Assessment of the efficacy of commercial porcine reproductive and respiratory syndrome virus (PRRSV) vaccines based on measurement of serologic response, frequency of gamma-IFN-producing cells and virological parameters of protection upon challenge. cord-010094-t0y3t9v3 2020 [32, [36] [37] [38] [39] [40] [41] [43] [44] [45] [46] [47] In this study, a kind of highly biocompatible Gly-CDs was synthesized from active ingredient of Chinese herbal medicine, which combines the high biocompatibility of CDs with the excellent antiviral properties of glycyrrhizic acid and inhibit the proliferation of PRRSV by ≈5 orders of magnitude. According to the experimental design (Scheme S1, Supporting Information), the addition of Gly-CDs significantly reduced PRRSV titers in intracellular and cell supernatants at 12, 24, 36, and 48 h post infection (hpi), with a maximal reduction of ≈10 5 -fold by plaque assay (Figure 3a,b) , demonstrating the strong antiviral effect of Gly-CDs on PRRSV. Adsorption Assay: MARC-145 cells were precooled at 4 °C for 30 min, followed by infection with PRRSV (MOI = 0.001) for 2 h at 4 °C in the presence of 0.30 mg mL −1 Gly-CDs in DMEM (containing 2% FBS). cord-012909-o6t2srim 2020 Both virulent and live-attenuated porcine reproductive and respiratory syndrome virus (PRRSV) strains can establish persistent infection in lymphoid tissues of pigs. In this study, expression of several important chemokine ligands (CCL19, CCL21, CCL24, CCL22, CX3CL1, and CCL14) and chemokine receptors (CCR6 and CCR10) which play an essential role in migration and localization of lymphocytes and antigen-presenting cells (APCs) to the lymphoid tissues was down regulated in ILN of CON90-infected pigs (Figure 6a ). In this study, expression of several important chemokine ligands (CCL19, CCL21, CCL24, CCL22, CX3CL1, and CCL14) and chemokine receptors (CCR6 and CCR10) which play an essential role in migration and localization of lymphocytes and antigen-presenting cells (APCs) to the lymphoid tissues was down regulated in ILN of CON90-infected pigs (Figure 6a ). GO terms and KEGG analysis revealed that genes involved in the innate immune (complement and TLR) pathways, apoptosis, cytokine-chemokine signaling, T-cell exhaustion, and humoral responses are highly differentially expressed in PRRSV-infected animals compared to control. cord-029839-jxqi9exm 2019 Conversely, the mRNA level of PRRSV in shRNA treated Tp-PBMCs dramatically decreased, and there were significant increases of the transcription of immune genes, such as interleukin-2 (IL-2), interleukin-4 (IL-4), interferon-alpha (IFN-α), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), toll-like receptor 3 (TLR3), toll-like receptor 7 (TLR7), Myeloid differentiation primary response gene (88) (MyD88), and interleukin-27p28 (IL-27p28). Therefore the knockdown of TGF-β1 gene expression by shRNA not only inhibits the replication of PRRSV but also improves immune responsiveness following viral infection, suggesting a novel way to facilitate the control of PRRSV infection in pigs. As Table 3 The relative mRNA levels of immune genes in Tp-PBMCs transfected with shTFGβ1-1 and pNeg plasmid and cultured for 48 h. Our experiment firstly screened out effective specific shRNA targeted to pig TGF-β1 gene, it could significantly knock down the mRNA level of TGF-β1 gene and obviously increase the viability of PRRSV infected cells. cord-033692-txfuuu7d 2020 cord-252339-l3si3jpn 2010 cord-255793-fi1vo0gx 2015 cord-255828-jrqdyfbg 2012 cord-255857-y9wjp0aj 2001 Two full-length porcine reproductive and respiratory syndrome virus (PRRSV) genomes, strain VR-2332 and its cell culture passaged descendent RespPRRS vaccine strain, were compared and analyzed in order to identify possible sites of attenuation. However, the cluster of amino acid mutations located near the carboxyl terminal end suggests that the replicase region was altered during passage to result in a more fit virus for replication in cell culture, as evidenced by the in vitro one-step growth curve comparison shown in Fig. 4 . Sequence analysis of strains VR-2332 and RespPRRS indicated that there were 15 nucleotide changes in this region, and all but one of which resulted in amino acid alterations. Attenuation can result from changes in many areas of viral genomes and the 41 nucleotide mutations described include alterations in several key PRRSV regions. cord-257220-fe2sacjj 2014 LDV elevates IgG levels in mice with little production of virus-specific antibodies [11, 21] , which is almost identical to what is seen in isolator piglets infected with PRRSV [22] (''''The effect of age, rearing, complement and the role of mucosal immunity'''' section). Polyclonal activation of B cells occurs in lymphoid organs from porcine reproductive and respiratory syndrome virus (PRRSV)-induced pigs The presence of alpha interferon at the time of infection alters the innate and adaptive immune responses to porcine reproductive and respiratory syndrome virus Interferon type I response in porcine reproductive and respiratory syndrome virus-infected MARC-145 cells Antigen-specific B cell responses to porcine reproductive and respiratory syndrome virus infection Antibody production and blastogenesis response in pigs experimentally infected with porcine reproductive and respiratory syndrome virus Neutralizing antibody responses of pigs infected with natural GP5 N-glycan mutants of porcine reproductive and respiratory syndrome virus cord-257886-ytlnhyxr 2019 title: Nucleocapsid protein of porcine reproductive and respiratory syndrome virus antagonizes the antiviral activity of TRIM25 by interfering with TRIM25-mediated RIG-I ubiquitination These results indicate for the first time that TRIM25 inhibits PRRSV replication and that the N protein antagonizes the antiviral activity by interfering with TRIM25-mediated RIG-I ubiquitination. The cells were lysed in RIPA lysis buffer after 36 h of transfection and the effects of siRNAs were analyzed by WB using an anti-TRIM25 monoclonal antibody (cat. To investigate whether TRIM25-mediated RIG-I ubiquitination is regulated by the PRRSV N protein, HEK293T cells grown in 6-well plates were co-transfected with pCAGGS-Flag-RIG-I (0.5 μg per well) and HA-ubiquitin (0.5 μg per well), and the indicated amounts of the Myc-N expression plasmids. The experiment revealed that TRIM25-mediated RIG-I ubiquitination was potentiated by Sendai virus (SEV) infection but was substantially suppressed by increasing the PRRSV N protein expression, in a dose-dependent manner (Fig. 5) . cord-258536-qnn9hp8e 2017 cord-259296-qsaewje2 2020 cord-259771-653opx0h 2012 In a pre-challenge study, intranasal delivery of Nano-KAg resulted in induction of innate immune response at both mucosal and systemic sites, indicated by a significant increase in the frequency of NK cells, DCs, and cd T cells in the lung MNC ( Figure 2 , A-C); and cd T cells and DCs in the PBMC compared to K-Ag vaccinated pigs (Figure 2, H & I) . Lung homogenates of Nano-KAg immunized pigs contained significantly higher levels of virus specific IgA and IgG antibodies compared to unvaccinated and K-Ag vaccinated, MN184 challenged pigs (Figure 4, A & B) . The frequency of cd T cells and CD4 + (but not CD8 + ) T cells in the lungs of Nano-KAg vaccinated animals were significantly increased compared to K-Ag and unvaccinated, virus challenged pigs ( Figure 5 , D, E & F). cord-260840-tudl9k1g 2012 More recently, attention has focused on the occurrence of high mortality in Chinese swine herds which Veterinary Microbiology 158 (2012) [69] [70] [71] [72] [73] [74] [75] [76] [77] [78] [79] [80] [81] To determine differences in infection kinetics of two temporally and genetically different type 2 porcine reproductive and respiratory syndrome virus (PRRSV) isolates in vivo with and without concurrent porcine circovirus (PCV) type 2a or 2b infection, 62 pigs were randomly assigned to one of seven groups: negative controls (n = 8); pigs coinfected with a 1992 PRRSV strain (VR-2385) and PCV2a (CoI-92-2a; n = 9), pigs coinfected with VR-2385 and PCV2b (CoI-92-2b; n = 9), pigs coinfected with a 2006 PRRSV strain (NC16845b) and PCV2a (CoI-06-2a; n = 9), pigs coinfected with NC16845b and PCV2b (CoI-06-2b; n = 9), pigs infected with VR-2385 (n = 9), and pigs infected with NC16845b (n = 9). cord-261160-g92zhv19 2003 title: Lymphoid tissue tropism of porcine reproductive and respiratory syndrome virus replication during persistent infection of pigs originally exposed to virus in utero Even though PRRSV-specific antibody appears as early as 5 days post-infection and is followed by serum neutralizing activity and cell-mediated immunity Molitor, 1997, 1999; Rowland et al., 1999 Rowland et al., , 2001 persistently infected pigs can continue to shed virus. The purpose of this study was to further understand persistent infection in congenitally infected pigs by characterizing the course of clinical disease, sites of virus replication and the capacity to transmit virus in a group of pigs exposed to PRRSV in utero. Analysis of virus and antibody in blood and/or umbilical cords from the 28 live neonates showed that at least 20 or 74% were virus isolation (VI) or RT-PCR positive for PRRSV at the time of farrowing indicating that in utero infection was successful. cord-262021-emboxdzu 2012 cord-262347-ejhz9rra 2015 The nidovirus order constitutes a group of singlestranded positive-sense RNA viruses which share a hallmark replication/transcription strategy, similar genomic organization, and a defining set of genetic elements, but differ in host species and range, disease phenotype, virion morphology, cellular tropism, genomic size and encoded content . It has been shown that the EAV replicase proteins (ORF1a/b) are sufficient to support viral replication (Molenkamp et al., 2000b) , but that infectivity is dependent on the presence of the structural genes encoded at the 3 0 -end of the arterivirus genome Molenkamp et al., 2000b; Verheije et al., 2002) . Leader-body junction sequence of the viral subgenomic mRNAs of porcine reproductive and respiratory syndrome virus isolated in Taiwan Molecular cloning and nucleotide sequencing of the 3 0 -terminal genomic RNA of the porcine reproductive and respiratory syndrome virus Comparison of the 5 0 leader sequences of North American isolates of reference and field strains of porcine reproductive and respiratory syndrome virus (PRRSV) cord-264598-2u8bm2fz 2020 cord-266199-smlq11y9 2019 cord-266716-pghnl980 2018 title: Isobavachalcone inhibits post-entry stages of the porcine reproductive and respiratory syndrome virus life cycle Since the first report of a porcine reproductive and respiratory syndrome (PRRS) outbreak, tremendous efforts to control this disease, including various national policies and plans incorporating the use of multiple modified live-virus vaccines, have been made. Western blot analysis revealed that PRRSV N protein levels decreased markedly, indicating that increasing concentrations of IBC significantly inhibited PRRSV replication (Fig. 1F) . The in vitro study established that IBC efficiently inhibited the replication of both HP-PRRSV and the current Chinese epidemic NADC30-like strains without significant drug toxicity. Role of phosphatidylinositol 3-kinase (PI3K) and Akt1 kinase in porcine reproductive and respiratory syndrome virus (PRRSV) replication Pathogenicity and antigenicity of a novel NADC30-like strain of porcine reproductive and respiratory syndrome virus emerged in China NADC30-like strain of porcine reproductive and respiratory syndrome virus cord-269560-vq462fh2 2017 cord-270688-g703hhm4 2020 In order to investigate enterobacteria presence involved in the secondary infections in Porcine Reproductive and Respiratory Syndrome (PRRS) pigs with different viral co-infections, we identified enterobacteria for guiding clinical treatment. Approximately 13 types of bacteria were successfully isolated from lung, spleen, liver, kidney and lymph node samples of different PRRS pigs. Enterobacteria were isolated in 100% of lung, liver and lymph samples from pigs infected with PRRSV alone. In the PRRSV alone infection group, enterobacteria were detected with a 157 100% positive rate in lung, liver and lymph samples, whereas in the co-infection group with 158 more than 3 types of virus species, the isolation rates in lung, liver, kidney and lymph were 159 significantly decreased. Secondary infection with Streptococcus suis serotype 7 increases the 291 virulence of highly pathogenic porcine reproductive and respiratory syndrome virus in pigs Pathogenesis of porcine reproductive and respiratory syndrome virus infection in 322 gnotobiotic pigs cord-272729-nbgdmavr 2012 Investigations into the mechanism of action of ribavirin against PRRSV and PEDV revealed that the addition of guanosine to the ribavirin treatment significantly reversed the antiviral effects, suggesting that depletion of the intracellular GTP pool by inhibiting IMP dehydrogenase may be essential for ribavirin activity. Further experiments revealed that suppression of ribavirin affects post-entry steps of the replication cycle of PRRSV and PEDV, including viral genomic and sg RNA synthesis, viral protein expression, and virus production. Several mechanisms of action for the antiviral activity of ribavirin have been suggested, including a reduction in cellular GTP pools via inosine monophosphate dehydrogenase (IMPDH) inhibition and increased mutation frequency on the virus genome leading to error catastrophe (Graci and Cameron, 2006) . Treatment of cells with ribavirin resulted in significant attenuation of postentry steps during the replication of porcine nidovirus, as determined by lower progeny production, diminished viral protein expression, and decreased synthesis of genomic RNA and sg mRNA. cord-275182-cmjfqkjz 2010 cord-275403-g4rohhtt 2002 To examine characteristics of putative nonstructural proteins (nsp) encoded in ORF1b, which have been identified by nucleotide similarity to domains of equine arteritis virus, defined genomic regions were cloned and expressed in the pRSET expression system. As initial proof of helicase-like activity, experiments were performed to test the ability of purified PRRSV-14 nsp10 protein to hydrolyze radiolabeled ribonucleotides in the presence or absence of polyribonucleotides. To further analyze the predicted helicase activity of the PRRSV nsp10 protein, experiments were performed using duplex substrates prepared with synthetic oligonucleotides containing single-strand regions at the 3Ј or 5Ј ends and short duplex regions (21 and 24 bp). The 5Ј-to-3Ј orientation of the unwinding activity of the PRRSV helicase was further confirmed in experiments using substrates prepared with in vitro transcribed RNA that contained singlestrand regions at the 5Ј end of both strands and duplex regions of 67 bp (5Ј5ЈDuplex #1) and 85 bp (5Ј5ЈDuplex #2), as shown in Fig. 9B . cord-275413-e2rhioty 2010 cord-275570-i9fw0afj 2018 cord-280578-4yxda0mf 2007 Viruses of the order Nidovirales regulate their genome expression by synthesizing two multidomain precursor polyproteins that are subsequently cleaved into functional viral proteins mainly by the 3CL protease (den Boon et al., 1991; Birtley et al., 2005; Snijder et al., 1996; van Aken et al., 2006) . The amplified DNA fragment encoding the PRRSV 3CL protease was inserted into the GST-fusion expression vector pGEX-6p-1 (GE Healthcare) with SmaI/XhoI sites (introduced by PCR primers). For protein expression, the plasmid was transformed into Escherichia coli strain BL21 (DE3) competent cells and the single colony was inoculated into Luria-Bertani (LB) medium with 50 mg l À1 ampicillin (Sigma, USA) at 310 K for overnight growth. For crystallization, the purified protein was concentrated to approximately 20 mg ml À1 and the buffer was exchanged to 10 mM Tris-HCl, 10 mM NaCl, 1 mM EDTA, 1 mM DTT pH 7.5. cord-281309-c9y7m5do 2013 We found that this HP-PRRSV strain caused extreme morbidity, as was seen in Asia, but novel to this study, resulted in up to 100x higher abundance of circulating virus when compared to VR-2332, caused extremely exacerbated thymic atrophy such that the thymus was often difficult to discern, and the host response was assessed in comparison to animals infected with strain VR-2332 for the first time by a swine protein array including 5 innate and 5 adaptive cytokines in serum, bronchoalveolar lavage fluid and lymph nodes. It was demonstrated that infection with a highly pathogenic strain of PRRSV elicited a significant elevation of all adaptive immunity cytokines measured in BALF, as well as a majority of these cytokines in serum and TBLN homogenates of the same groups of pigs. cord-281676-yy5etfek 2011 Consistent with the reduced lung lesions and viremia, a significantly increased frequency of IFN-␥Table 1 Frequency of immune cells in pigs inoculated intranasally with mock (no vaccination and no challenge), unvaccinated (n = 9) or vaccinated with PRRS-MLV+ Mtb WCL (n = 9) and then challenged with PRRSV MN184. Evaluation of the frequency of various immune cells at both mucosal (lung and TBLN MNC) and systemic sites (PBMC) in vaccinated and virulent PRRSV challenged pigs is important for associating cytokine responses. In our study, a consistently reduced frequency of Tregs in the lungs, blood, and TBLN of pigs vaccinated intranasally with PRRS-MLV+ Mtb WCL was detected which was associated with reduced secretion of both the immunosuppressive cytokines, IL-10 and TGF-␤. Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs cord-282113-sed5xyte 2010 In this paper, we have used porcine reproductive and respiratory syndrome virus (PRRSV) as a model virus to address whether infectious mammalian virus particles can be generated in insect cells from recombinant baculovirus. To investigate whether PRRSV particles were generated following infection of insect cells with the recombinant baculovirus, sf9 cells were infected with AcAPRRS and supernatants were harvested 7 days later. We report that infection of insect sf9 cells with the recombinant baculovirus AcAPRRS led to the synthesis of PRRSV proteins and the culture supernatant contained particles that were morphologically indistinguishable from PRRSV virions. In this study, we have demonstrated that a recombinant baculovirus carrying PRRSV genomic cDNA was able to generate infectious PRRSV following transduction of mammalian cells that are themselves refractory to infection with PRRSV in vitro. When the recombinant baculovirus was inoculated onto insect sf9 cells or mammalian Vero and BHK-21 cells, infectious PRRSV virions were generated. cord-282242-5tkhjiwl 2009 title: Cytokine Expression by Macrophages in the Lung of Pigs Infected with the Porcine Reproductive and Respiratory Syndrome Virus The aim of the present study was to characterize the production of cytokines by subpopulations of pulmonary macrophages in pigs infected by the PRRS virus (PRRSV). Several studies have examined the role of cytokines in the pathogenesis of PRRS (Van Reeth and Nauwynck, 2000) ; however, it is not clear how cytokines participate in macrophage activation during PRRSV infection or how they regulate development of the immune response to the virus. The expression of IFN-g by macrophages and lymphocytes has been previously reported in the lung of PRRSV-infected pigs (Thanawongnuwech et al., 2003) . Therefore, the expression of IL-10 observed in the present study might be responsible for reduced expression of cytokines such as IFN-a, IFN-g, IL-12p40 and TNF-a, that in turn may impair prolonged viral replication in the lung of infected animals. cord-283689-dzin12qb 2019 cord-284076-087oltss 2007 cord-285746-ndrja7os 2020 cord-288669-46tkedw7 2006 cord-289152-w5ynbewh 2005 In porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells, NF-κB activation was characterized by translocation of NF-κB from the cytoplasm to the nucleus, increased DNA binding activity, and NF-κB-regulated gene expression. Taken together, these results demonstrated that PRRSV induces nuclear translocation of NF-nB followed by increased DNA binding activity of NF-nB both in MARC-145 cells and PAM cultures. To determine if NF-nB activation by PRRSV was dependent on InBa degradation in MARC-145 cells, the NF-nB pathway was blocked by using an adenovirus vector expressing a dominant negative form of InBa (Ad-InBaDN) which lacks both constitutive (Barroga et al., 1995) and inducible (Brown et al., 1995) phosphorylation sites. This study showed that PRRSV infection resulted in increased nuclear translocation of NF-nB and increased DNA binding activity both in MARC-145 cells and PAM cultures. cord-290775-w8ukokl7 2009 cord-291192-wm2eyaam 2014 cord-291962-rp172ugk 2019 title: Nucleotide-binding oligomerization domain-like receptor X1 restricts porcine reproductive and respiratory syndrome virus-2 replication by interacting with viral Nsp9 To test this, increasing dose of NLRX1 was transfected into Marc-145 cells followed by PRRSV infection, qPCR was then performed to test the total viral RNA levels. On the other hand, recent literature indicated that the interaction of Nsp9 with SUMO E2 conjugating enzyme Ubc9 and cellular protein interleukin-2 enhancer binding factor 2 (ILF2) through its RdRp domain resulted in a significantly decrease of virus titers, indicating that cells utilize host antiviral factors as defense mechanisms to limit PRRSV infection Wen et al., 2017) . An intracellularly expressed Nsp9-specific nanobody in MARC-145 cells inhibits porcine reproductive and respiratory syndrome virus replication Porcine reproductive and respiratory syndrome virus nucleocapsid protein interacts with Nsp9 and cellular DHX9 to regulate viral RNA synthesis The DEADbox RNA helicase 5 positively regulates the replication of porcine reproductive and respiratory syndrome virus by interacting with viral Nsp9 in vitro cord-293768-uijc6qdo 1997 cord-298131-zolwjl9u 2010 Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. To investigate the regulation of the host response to the N-PRRSV virus, we considered the global gene expression profiles in lungs using Solexa/Illumina''s DGE system, a tag-based transcriptome sequencing method. From the data presented in the paper, a model for the relationship between pulmonary gene expression profiles and infection pathology can be surmised in Figure 7 , N-PRRSV virus replicates and spreads by subverting host innate immune response and hijacking host lipid metabolism as well as inducing an antiapoptotic and anti-inflammatory state, as indicated by suppression expression of SPI IFN, IFN-a, down-regulation expression of proapoptotic genes for BAK, APR-1, SARP3, high levels expression of genes involved in lipid metabolism, such as APOE, LDLB, PIK3C3, anti-apoptotic genes for MCL1, BCL2A1, CHFR, ADM, NFKB, IL10, and anti-inflammatory molecule PGE2 as well as CD163. cord-299038-e0nsol3y 2020 Conversely, Siglec-1 is a macrophage phagocytic receptor that engages GBS and other sialylated bacteria to promote effective phagocytosis and antigen presentation for the adaptive immune response, whereas certain viruses and parasites use Siglec-1 to gain entry to immune cells as a proximal step in the infectious process. The interplay between a particular sialylated human pathogen, group B Streptococcus (GBS), and host immune responses serves as a good first example to illustrate the role of Siglecs and bacterial expression of Sia in the pathogenesis of infection. Importantly, in addition to Sia-dependent Siglec engagement, certain GBS strains can use the surface-anchored β protein to bind human Siglec-5, another inhibitory Siglec preferentially expressed on macrophages and neutrophils. Loss of Siglec-1 expression not only affected the macrophage sampling and trapping capabilities but also the production of anti-GBS antibodies, suggesting a key role in optimization of antigen presentation and subsequent adaptive immune response against sialylated pathogens (Chang et al. cord-299721-gm6nx84a 2014 cord-299751-2drhoz70 2016 The efficacy of a novel BEI-inactivated porcine reproductive and respiratory syndrome virus (PRRSV) candidate vaccine in pigs, developed at RIBSP Republic of Kazakhstan and delivered with an adjuvant Montanide™ Gel 01 ST (D/KV/ADJ) was compared with a commercial killed PRRSV vaccine (NVDC-JXA1, C/KV/ADJ) used widely in swine herds of the Republic of Kazakhstan. Clinical parameters (body temperature and respiratory disease scores), virological and immunological profiles [ELISA and virus neutralizing (VN) antibody titers], macroscopic lung lesions and viral load in the lungs (quantitative real-time PCR and cell culture assay) were assessed in vaccinated and both genotype 1 and 2 PRRSV challenged pigs. The challenge virus strains LKZ/2010 and CM/08 were propagated in MARC-145 cells, and confirmed as type 1 and type 2 viruses by EZ-PRRSV TM MPX 4.0 Real Time RT-PCR using Target-Specific Reagents kit for the Rapid Identification & Differentiation of North American and European PRRS Viral RNA (Tetracore, MD, USA). cord-301563-s0ypy2hf 2015 For example, human immunodeficiency virus 1 (HIV-1) prevents antiviral interferon response via Vpr-and Vif-directed, ubiquitin-mediated proteosomal degradation of interferon regulatory factor 3 (IRF-3) (Okumura et al., 2008) ; the papain-like protease (PLpro) domains of many coronaviruses, such as severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), human coronavirus NL63 (HCoV-NL63), and mouse hepatitis virus A59 (MHV-A59), have deubiquitinating (DUB) activity that blocks type I interferons (IFNs) induction (Barretto et al., 2005; Chen et al., 2007b; Clementz et al., 2010; Devaraj et al., 2007; Frieman et al., 2009; Lindner et al., 2005; Zheng et al., 2008) ; the leader proteinase (L pro ) of Foot-and-mouth virus (FMDV) acts as a deubiquitinase that cleaves ubiquitin chains from retinoic acid-inducible gene I (RIG-I), TANK-binding kinase 1 (TBK1), TNF receptor associated factor 6 (TRAF6), and TRAF3, thereby inhibiting the activation of type I IFN signaling ; the N-terminal protease (Npro) of bovine viral diarrhea virus interacts with IRF-3 and promotes its polyubiquitination and subsequent degradation through the proteasome (Chen et al., 2007a) ; the latency associated protein ORF73 of murid herpesvirus-4 (MuHV-4) associates with the host ubiquitin-ligase complex to promote poly-ubiquitination and subsequent proteasomal degradation of p65/RelA, which inhibits the activity of nuclear factor B (NF-B) to facilitate the establishment of MuHV-4 latency (Rodrigues et al., 2009) . cord-301692-zu0ubwfq 2007 cord-302306-fudeixy2 2020 Here, we report generation of double-gene-knockout (DKO) pigs harboring edited knockout alleles for known receptor proteins CD163 and pAPN and show that DKO pigs are completely resistant to genotype 2 PRRSV and TGEV. Additional infection challenge experiments showed that DKO pigs exhibited decreased susceptibility to porcine deltacoronavirus (PDCoV), thus offering unprecedented in vivo evidence of pAPN as one of PDCoV receptors. Through viral challenge experiments, we found that these DKO pigs exhibit complete resistance to genotype 2 PRRSV and TGEV, and exhibit decreased susceptibility to PDCoV infection. Thus, in addition to demonstrating that our DKO pigs are robustly resistant to both PRRSV and TGEV without suffering deleterious effects for production performance, our study also provides insights into ongoing controversy about the pAPN protein as a potential receptor for PDCoV infection of pigs. pAPN protospacer PAM In order to generate more DKO pigs for viral challenge experiments, we collected ear tissue samples from three piglets (#1143, #1144, and #1145) and isolated ear-derived fibroblasts. cord-306948-wkisfz1m 2014 cord-307073-vatfdilt 2004 cord-309428-qkjjxr6p 2015 MicroRNAs (miRNAs) play important roles in viral infections, especially by modulating the expression of cellular factors essential to viral replication or the host innate immune response to infection. To identify host miRNAs important to controlling porcine reproductive and respiratory syndrome virus (PRRSV) infection, we screened 15 miRNAs that were previously implicated in innate immunity or antiviral functions. Luciferase reporters showed that miR-26a does not target the PRRSV genome directly but instead affects the expression of type I interferon and the IFN-stimulated genes MX1 and ISG15 during PRRSV infection. We found that miR-26a does not target the PRRSV genome directly, but rather affects the expression of type I interferon and the IFN-stimulated genes MX1 and ISG15 during PRRSV infection. Indirect immunofluorescence assays (IFA) were performed as described previously (Tian et al., 2011) for the detection of nucleocapsid (N) protein in PRRSV vJX143 infected MARC-145 cells or PAMs pre-transfected with miR-26 family or mutant mimics. cord-310771-tnwfp1je 2005 A method was developed for qualitative and quantitative detection of the seminal cell-associated PRRSV RNA in relation to endogenous and exogenous reference RNAs. As endogenous control for one-step real-time reverse transcription (RT)-PCR UBE2D2 mRNA was selected. Particularly for the analysis of persistent infections associated with low copy numbers of PRRSV RNA, UBE2D2 mRNA is an ideal control due to its low expression in seminal cells and its detection in all samples analysed (n = 36). For the development of one-step real-time RT-PCR for four endogenous reference RNAs (HPRT, UBE2D2, PPIA, and HMBS) appropriate target regions were selected and the assay conditions were optimised for amplification efficiency. One-step real-time RT-PCR assays for PRRSV-1 and -2 RNA allowed quantitation with optimal efficiency (Fig. 1a ; standard curves for two additional viremic pigs infected with PRRSV-1 (data not shown)) as achieved for endogenous and Fig. 1 . cord-312208-8ydh6jev 2000 cord-312787-j7ye7ed5 1996 coli-expressed ORFs 5 to 7 gene products, suggested that antibodies directed against the envelope E protein appear by day 7 p.i., whereas antibodies directed against the nucleocapsid N and membrane M proteins can only be detected by the end of the second week p.i. No correlation could be demonstrated between VN and IIF antibody titers, viremia, and viral protein specificities of circulating antibodies at various times p.i. Summary. coli-expressed ORFs 5 to 7 gene products, suggested that antibodies directed against the envelope E protein appear by day 7 p.i., whereas antibodies directed against the nucleocapsid N and membrane M proteins can only be detected by the end of the second week p.i. No correlation could be demonstrated between VN and IIF antibody titers, viremia, and viral protein specificities of circulating antibodies at various times p.i. The porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped RNA virus which has been found to be responsible for reproductive failure in sows of any parities (late-term abortions, increased numbers of stillborn, mummified and weakborn pigs) and respiratory problems affecting pigs of all ages [8, 20] . cord-313445-4v7pjqt2 2020 title: Porcine interferon lambda 3 (IFN-λ3) shows potent anti-PRRSV activity in primary porcine alveolar macrophages (PAMs) In addition, IFN-λ3 in our study was able to induce the expression of interferon-stimulated genes 15 (ISG15), 2′-5′-oligoadenylate synthase 1 (OAS1), IFN-inducible transmembrane 3 (IFITM3), and myxoma resistance protein 1(Mx1) in primary PAMs. CONCLUSIONS: IFN-λ3 had antiviral activity against PRRSV and can stimulate the expression of pivotal interferon-stimulated genes (ISGs), i.e., ISG15, Mx1, OAS1, and IFITM3. The virus titre was significantly reduced with the increase of IFN-λ3 treatment dose (10, Fig. 1 The CPE of primary PAMs treated with Porcine IFN-λ3 and infected with PRRSV. The expression of mRNA for ISG15, Mx1, OAS1, and IFIT M3 was up-regulated by 70, 70, 160, and 15 times respectively at the concentration of 1000 ng/ml in primary PAMs. As shown in Fig. 3e and f (The full-length blots are presented in Supplementary file 2), a dosedependent induction of the antiviral proteins ISG15, Mx1 and OAS1 has been observed in primary PAMs treated with IFN-λ3. cord-319779-n5w1f0rr 2004 North American porcine reproductive and respiratory syndrome virus (PRRSV) field isolates were studied with regard to IFN-α sensitivity and induction in order to understand the role of type I IFN in PRRSV pathogenesis. PRRSV isolates were differentially sensitive to porcine recombinant IFN-α (rIFN-α) and varied in their ability to induce IFN-α in porcine alveolar macrophages (PAM) cultures as measured by a porcine IFN-α specific ELISA on cell culture supernatants. In this study, North American field isolates of PRRSV were evaluated with respect to induction, sensitivity and suppression of an in vitro type I IFN response. UV-inactivated PRRSV stocks were tested to determine whether virus binding to the cells is responsible for enhanced IFN-a production by polyI:C in cells infected with isolate 3 (Fig. 6) . In this study, North American PRRSV field isolates were evaluated with respect to induction, sensitivity and suppression of an in vitro IFN response in PAM cultures. Immune responses in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) cord-321195-cndq6aqb 2014 cord-321471-gev5xq3a 2013 cord-322593-bgm6smuo 2016 cord-324495-0pee1i3o 2015 cord-324950-ux7shvji 2020 In pigs, the term "Porcine Respiratory Disease Complex" (PRDC) is often used to describe coinfections involving viruses such as swine Influenza A Virus (swIAV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), and Porcine CircoVirus type 2 (PCV2) as well as bacteria like Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae and Bordetella bronchiseptica. The outcome of any coinfection or superinfection can be affected by the interactions taking place between the infectious agents, the nature of the cell/host, adverse environmental and management conditions, intestinal and respiratory microbiomes, and the triggered immune response-innate and adaptive-developed afterwards [2, 3] . It is well-known that viral infections can induce an ideal environment for a bacterial superinfection through different mechanisms such as the destruction of the epithelial barrier, the over-expression of the receptors involved in the bacterial adhesion to the cells, and the alteration of the host immune response [1, 2, 94, 95] . cord-325875-93krp81r 2020 (2020) showed that the probability of detecting porcine reproductive and respiratory syndrome virus (PRRSV) ribonucleic acid (RNA) in serum by reverse transcription polymerase chain reaction (RT-PCR) at 98 days post infection (DPI) was~2% versus~30% in lymphoid tissues (tonsil) by bioassay [16] . Similarly, differences in detection rates have been reported for pen-based oral fluids versus individual Table 1 provides examples of the detection of virus-specific nucleic acids and/or antibody in swine oral fluids, i.e., is not comprehensive b Acronyms defined in the list of abbreviations and terms pig buccal or nasal swabs for animals inoculated with FMDV, IAV, Senecavirus A (SVA), and swine vesicular disease virus (SVDV) [45, 62, 63, 68] . Diagnosis of the Lelystad strain of porcine reproductive and respiratory syndrome virus infection in individually housed pigs: comparison between serum and oral fluid samples for viral nucleic acid and antibody detection cord-328935-mn8r972x 2015 Studies of the potential of novel adjuvants to improve vaccine efficacy against genetically unstable, immune-subverting RNA viruses, such as porcine reproductive and respiratory syndrome virus in pigs, should assist in the control of pathogens with similar characteristics in other species. However, a recent study showed that an inactivated reassortant RV strain (CDC-9 strain) formulated with aluminum phosphate and administered systemically in gnotobiotic pigs resulted in induction of serum IgG antibody titers, coinciding with partial protection against shedding and diarrhea, suggesting that adjuvant may have stimulated local specific (gut IgA antibodies) or nonspecific immune responses, which were not assessed in this study (Wang et al., 2010) . Intranasal delivery of whole cell lysate of Mycobacterium tuberculosis induces protective immune responses to a modified live porcine reproductive and respiratory syndrome virus vaccine in pigs cord-329274-ncvvmkca 2002 cord-329625-hx2rsi91 2008 title: A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, in common with many other positive strand RNA viruses, encodes a nucleocapsid (N) protein which can localise not only to the cytoplasm but also to the nucleolus in virus-infected cells and cells over-expressing N protein. To investigate whether the trafficking of N protein between the cytoplasm and the nucleus/nucleolus was associated with microtubules or energy dependent, the mobility of EGFP-PRRSV-N protein was compared in 3D4/31 cells incubated at 37°C in the presence and absence of nocodazole (60ng/ml nocodazole (Sigma) for 16h), a microtubule inhibitor, or incubated at 10°C. In approximately 10% of cells expressing EGFP-PRRSV-N protein fluorescence was observed in the cytoplasm, but only if imaging was adjusted so that the fluorescent signal in the nucleus/nucleolus was above the linear range (for example Fig. 8C, lower panels) . cord-330035-0d6w8xyd 2017 cord-332049-geh9aaf5 2010 Pulmonary dysfunction was evaluated in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV, isolate VR-2332) and compared to clinical and pathological findings. A combination of impulse oscillometry and rebreathing of test gases can be used to evaluate lung ventilation, respiratory mechanics and pulmonary gas exchange in spontaneously breathing pigs. Pulmonary function tests (PFTs) were performed twice before challenge (À7 and À3 days) and seven times after challenge (2, 4, 6, 9, 12, 15, 18 and 21 dpi) in eight pigs exposed to PRRSV and in eight controls (Table 1) . M. hyopneumoniae, Mycoplasma hyopneumoniae; APP, Actinobacillus pleuropneumoniae; PCV-2, porcine circovirus type 2; PRCV, porcine respiratory coronavirus; SIV, swine influenza virus; TGEV, transmissible gastroenteritis virus; PFT, pulmonary function tests (8 pigs per group examined postmortem at 21 dpi). Pulmonary function tests in PRRSV challenged pigs indicate both obstructive and restrictive disorders (confirmed by increased Rrs at frequencies 65 Hz and decreased Xrs), as well as disorders in gas exchange (confirmed by decreased TL CO Hb ). cord-332154-2gej7h1d 2004 Immunization of pigs with a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine initially elicits a weak interferon (IFN)-γ response. Based on the success of this intervention and the noted absence of IFN-a generation during PRRSV infection, the present studies were undertaken to determine if the antiviral adaptive immunity induced by vaccination with PRRS MLV could be modified simply by the co-administration of rIL-12 protein directly, or of either porcine IFN-a or IL-12 indirectly via plasmids expressing these cytokines. Although a similar response was evident during this time period for vaccinated pigs also i.m. injected with exogenous IL-12 either directly as protein or indirectly via IL-12 cDNA, immunized animals that were i.d. inoculated with IL-12 cDNA exhibited an overall 2.7-fold transient increase in the frequency of PRRSV-specific IFN-g SC at 2 weeks post-vaccination. Immune responses in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) cord-333349-tsfxpaj6 2014 cord-333423-jhm7u8ka 2019 Furthermore, the nsp11-IRF9 interaction impaired the formation and nuclear translocation of the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) in both nsp11-overexpressed and PRRSV-infected cells. Taking the results together, our study demonstrated that PRRSV nsp11 antagonizes type I IFN signaling by targeting IRF9 via a NendoU activity-independent mechanism, and this report describes a novel strategy evolved by PRRSV to counteract host innate antiviral responses, revealing a potential new function for PRRSV nsp11 in type I IFN signaling. The type I IFN-activated ISGF3 transcription complex containing tyrosine-phosphorylated STAT1 and STAT2 associated with IRF9 is rapidly translocated to the nucleus FIG 3 PRRSV nsp11 inhibits ISGF3-induced ISRE promoter activity. This provided further support for the notion that the ability of PRRSV nsp11 to block type I IFN signaling is independent of its endoribonuclease activity and cell cytotoxicity, because these three mutants had similar effects with respect to inhibiting the formation and nuclear translocation of ISGF3 compared with WT nsp11. cord-335706-lopcb77c 2011 cord-335955-2bw2sly8 2016 cord-340422-8f5xe4zc 2001 cord-342276-zrsnahi7 2011 title: Cellular membrane cholesterol is required for porcine reproductive and respiratory syndrome virus entry and release in MARC-145 cells In this study, the role of the plasma membrane cholesterol in porcine reproductive and respiratory syndrome virus (PRRSV) infection of MARC-145 cells was investigated. Previous studies demonstrated that plasma membrane cholesterol plays an important role in the entry and infection processes of many viruses, especially in some enveloped viruses [21] , including Human immunodeficiency virus type 1 (HIV-1) [22] , Poliovirus [23] , Murine coronavirus [24] , Vaccinia virus [25] , Herpes simplex virus [26] , Foot-and-mouth disease virus [27] , and Severe acute respiratory syndrome-related coronavirus (SARS-CoV) [28] . Altogether, these data indicated that cellular membrane cholesterol was required for PRRSV entry into MARC-145 cells, and its depletion by MβCD mainly affects virus attachment, rather than penetration. cord-344410-yo9libo0 2011 cord-344740-st2yw090 2004 cord-344953-gtg12hiu 2017 cord-345516-fgn7rps3 2012 cord-350626-ov9fy10b 2020 cord-351881-qea4b0i5 2016 title: Virus replicon particles expressing porcine reproductive and respiratory syndrome virus proteins elicit immune priming but do not confer protection from viremia in pigs However, none of the PRRSV antigens expressed from VRP, with the exception of the N protein, did induce any detectable antibody response in pigs before challenge infection with PRRSV. These data show that the VSV replicon vector can induce immune responses to heterologous proteins in pigs, but that the PRRSV envelope proteins expressed from VSV VRP are poorly immunogenic. Again, before challenge infection, vaccination with VRP expressing the structural proteins of PRRSV did not induce any detectable antibody response against GP5, GP4 and GP3 as measured by ELISA (not shown). Following challenge infection, GP5-specific antibody responses were detected on day 7 pi in 2 out of 4 pigs, and all pigs vaccinated with VRP expressing the PRRSV proteins seroconverted to GP5 at day 11 pi (Table 3 ). cord-352967-y1fyke9u 2010 In this study, we investigated the inhibitory effect of NO on the infection by porcine reproductive and respiratory syndrome virus (PRRSV) in vitro and the role of NO in the defense against PRRSV. We found that the maximal inhibition effect of NAP on PRRSV replication was achieved upon treatment 1 h after virus infection and the virus yield was reduced by approximately 50 fold in the presence of 400 μM NAP. To date, NAP is only used as the negative control for SNAP to study the inhibitory effect of NO on virus replication in previous studies, and its antiviral activity was not reported. Unexpectedly, NAP, the "commonly used" negative control for NO-donor SNAP had a significant antiviral activity against PRRSV replication (Fig. 1a ) at low infectious dose (MOI=0.05). The inhibitory effect of NAP in Marc-145 cells was investigated by determining the kinetics of PRRSV production under different NAP treatments. cord-353703-u86ggw11 2019 cord-354730-hfau2odb 2014 cord-356197-js7l86fh 2011