# pos

id: cord-294429-isivkz8b
pos: NNP
token:
  https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/surveillanceand-case-definitions

lemma:
  https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/surveillanceand-case-definitions


# ent

id: cord-256156-mywhe6w9
type: CHEMICAL
entity:
  GlcNAc N J o u r n a l P r e p r o o f 11 deacetylase N sulfotransferase that N deacetylates and N sulfates N acetylglucosamine


id: cord-256156-mywhe6w9
type: DISEASE
entity:
  herpes simplex virus 1 entry Nidovirus sialate O acetylesterases evolution and substrate specificity of coronaviral and toroviral receptor destroying enzymes The sweet spot defining virus sialic acid


id: cord-008613-tysyq6o4
type: CELL_LINE
entity:
  AT6 6AT CCC ACT 6AT CT8 ABC TTC TCC CCA BAT BAG ATC AAT AA6 0 N 120 140 160 180 200 CTC ATA GAS ACA G6C CTS AAT ACT GTA 6A6 TAT TTT ACT TCC CAA CAA 8TC ACA 66A ACA TCC TCT CTT 66A AA6 AAT ACA ATA CCA CC 666 6TC ACA 66A CTA 0 Leu He 6 u Thr 220 440 460 480 500 520 ACA TTA CCA TCA 66A TCC TAT ARE 666


id: cord-008613-tysyq6o4
type: PROTEIN
entity:
  HN hemagglutinin neuraminidase protein Mr 70 000 NP nucleoprotein Mr 61 000 P phosphoprotein Mr 44 000 M matrix protein Mr 38 000 V protein V Mr 24 000 polypeptide


id: cord-008613-tysyq6o4
type: DNA
entity:
  human parainfluenza virus type 3 patterns of amino acid sequence homology among paramyxovirus proteins Sequence


id: cord-253259-hmn7mg8j
type: DNA
entity:
  simian rotavirus SAll genome segment 3 product Rotavirus proteins VP7 NS28 and VP4 form oligomeric strucutres Sequence


id: cord-284944-hcgfe9wv
type: DNA
entity:
  GUS F GAAAATATGTGGTTGGAGAGCTCATT R CCGAGTGAAGATCCCCT TTTTA HPRT F GGACAGGACTGAACGTCTTGC R CTTGAGCACACAGAGGGCTACA S100A8 F CAACACTG ATGGTGCAGTTAACTTC R CTGCCACGCCCATCTTTATC S100A9 F CTGAGCTTCGAGG AGTTCATCA R CGTCACCCTCGTGCATCTTC Table 6


id: cord-284944-hcgfe9wv
type: PROTEIN
entity:
  CCL1 CCL11 CCL13 CCL15 CCL17 CCL19 CCL2 CCL20 CCL21 CCL22 CCL23 CCL24 CCL25 CCL26 CCL27 CCL3 CCL7 CCL8 CX3CL1 CXCL1 CXCL10 CXCL11 CXCL12 CXCL13 CXCL16 CXCL2 CXCL5 CXCL6 CXCL8 CXCL9 GM CSF IFNα IL 10 IL 16 IL 1b IL 2 IL 4 IL 6 MIF TNFa


id: cord-266480-u8o4eitu
type: PERSON
entity:
  Declaration of Interests Declaration of Interests Declaration of Interests Declaration of Interests P C S


id: cord-266480-u8o4eitu
type: ORG
entity:
  the Society for Public Health Education Statistical Inference for Partially Observed Markov Processes


id: cord-271032-imc6woht
type: GGP
entity:
  IFI6 IFIT1 HERC5 OASL MX1 IFIH1 IFI44 IFI44L OAS2 SERPINB1 IL1R2 SERPING1 CD163 RNASE1 IFI16 OAS3 ADAR LGALS3BP SPI1 DEFA3 DEFA4 HSP90AA1


id: cord-287349-1zcq7kzx
type: WORK_OF_ART
entity:
  Thinking Outside the Triangle Replication Coronavirus RNA Synthesis and Processing Continuous and Discontinuous


id: cord-269023-g21a9ik2
type: CHEMICAL
entity:
  Gormsen 1942 Drawing on this early work Max Cooper a young biologist working with Robert Good in Minnesota followed the trail of a report first published in a poultry


id: cord-270082-byxd4o4m
type: PROTEIN
entity:
  CTF73 protein SSPSS amino acids 224 228 Figure 8 Analysis Lechner and Carbon 1991 have described a multiprotein complex CBF3


id: cord-270082-byxd4o4m
type: DNA
entity:
  s9 ctf6 16 ctf9 67 ctfll 16 ctfl2 s30 ctf13 42 ctfl4 YPH960 MATa his3 A200 ade2 101 lys2 801 leu2 Al cdl 124 CFVll RADLd YPtf 275 URA3 SUP1 1 61 ctflir YPH961 MATa 6 3 52 lys2 801 adeB 101 his3 A200 trpl A 1 leulA 1 ctf18 160 CFlll CEN3 L YPH278 URA3


id: cord-270082-byxd4o4m
type: DNA
entity:
  yeast centromere DNAs Cell 29 235 244 Funk M Hegemann J and Philippsen P 1969 Mellor J Jiang W Funk M Rathjen J Barnes C Hiz T Hegemann J and Philippsen P 1990 CPFl


id: cord-270082-byxd4o4m
type: DNA
entity:
  budding yeast Saccharomyces cerevisiae J Cell Biol 109 3355 3388 Perier F and Carbon J 1992 A colony color


id: cord-270082-byxd4o4m
type: CELL_LINE
entity:
  yeast S cerevisiae J Cell Sci 22 219 242 Pluta A F Cooke C A and Earnshaw W C 1990 Structure of the human centromere


id: cord-294429-isivkz8b
type: DISEASE
entity:
  autoimmune disease diabetes kidney or liver disease congestive heart failure malignancy coagulopathy hepatitis B


id: cord-291790-z5rwznmv
type: WORK_OF_ART
entity:
  N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of 632 HIV 1 to Neutralizing Monoclonal Antibodies


id: cord-305290-xnjwv0d7
type: DNA
entity:
  7 nucleotide minimal site Cell 62 000 000 Chambers I Frampton J Goldfarb P Affara N McBain W and Harrison P R 1986


id: cord-279463-bli8hwda
type: CHEMICAL
entity:
  N linked glycosylation in the CAT protein After protease digestion in the presence of microsomal membranes


id: cord-295894-us5x1jtg
type: PROTEIN
entity:
  HSL hormone sensitive lipase PPAR peroxisome proliferator activated receptors DIO2 deiodinase type 2 β AR


id: cord-295894-us5x1jtg
type: PROTEIN
entity:
  adrenergic receptor ALDH1 aldehyde dehydrogenase isoform 1 PCK1 phosphoenolpyruvate carboxykinase 1 PI3K phosphatidylinositol 3 kinases MAPK mitogen activated protein kinase ERK extracellular regulated kinase


id: cord-295894-us5x1jtg
type: PROTEIN
entity:
  membrane and intracellular proteins e g peroxisome proliferator activated receptors PPARs hormone sensitive lipase HSL and 3


id: cord-295894-us5x1jtg
type: GGP
entity:
  PCK1 phosphoenolpyruvate carboxykinase 1 PI3K phosphatidylinositol 3 kinases MAPK mitogen activated protein kinase ERK extracellular


id: cord-295894-us5x1jtg
type: GGP
entity:
  peroxisome proliferator activated receptors PPARs hormone sensitive lipase HSL and 3 regulate tissue and


id: cord-302020-ypsh3rjv
type: DNA
entity:
  mouse hepatitis virus genus betacoronavirus subfamily Coronavirinae Irigoyen et al 2016 HCoV 229E genus alphacoronavirus subfamily


id: cord-302020-ypsh3rjv
type: DNA
entity:
  SJfilterCountTotalMin 1 1 1 1 outSJfilterDistToOtherSJmin 0 0 0 0 outFilterMismatchNmax 999 outFilterMismatchNoverReadLmax 0 04 scoreGapNoncan À4 scoreGapATAC À4 chimOutType WithinBAM HardClip chimScoreJunctionNonGTAG 0 alignSJstitch MismatchNmax


id: cord-326916-bakwk4tm
type: WORK_OF_ART
entity:
  The Rate of Underascertainment of Novel Coronavirus 2019 nCoV Infection Estimation Using Japanese Passengers Data on Evacuation Flights


id: cord-301997-63160t7f
type: DNA
entity:
  5 poly A leader date 1987 07 17 journal Cell DOI 10 1016 0092 8674 87 90212 1 sha bb790e8366da63c4f5e2d64fa7bbd5673b93063c doc_id 301997 cord_uid 63160t7f


id: cord-342189-ya05m58o
type: DISEASE
entity:
  influenza A encodes a protein that modulates mRNA splicing to degrade the mRNA that encodes RIG I Kochs


id: cord-336696-c3rbmysh
type: PROTEIN
entity:
  SnapShot COVID 19 Blake Oberfeld 1 Aditya Achanta 1 Kendall Carpenter 1 Pamela Chen 1 Nicole M Gilette 1 Pinky Langat 1 Jordan T Said 1 Abigail E Schiff 1 2 Allen S Zhou 1 Amy K Barczak 1 2


id: cord-339093-mwxkvwaz
type: ORG
entity:
  EM Structural Basis for Potent Neutralization of Betacoronaviruses by Single Domain Camelid Antibodies Identification of Human Single Domain Antibodies


id: cord-345103-b2wkm03g
type: PROTEIN
entity:
  SARS CoV 2 Spike Glycoprotein Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion Structure


id: cord-328289-3h3kmjlz
type: ORG
entity:
  the Nervous System Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease Pathological


id: cord-328289-3h3kmjlz
type: ORG
entity:
  the Frontlines Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease


id: cord-328289-3h3kmjlz
type: WORK_OF_ART
entity:
  Acute Hemorrhagic Necrotizing Encephalopathy Imaging Features Dysregulation of Immune Response in Patients With Coronavirus Immune


id: cord-350855-gofzhff7
type: RNA
entity:
  SFTPC 1220 mRNA alveolar type 2 cell marker localization in alveoli of a SARS CoV 2 autopsy 1221 55 lung SARS CoV 2


# url

id: cord-294429-isivkz8b
domain: www.who.int
url:
  http://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/surveillanceand-case-definitions


# bib

id: cord-008613-tysyq6o4
author: Thomas, Sheila M.
date: 1988-09-09
txt: ./txt/cord-008613-tysyq6o4.txt
cache: ./cache/cord-008613-tysyq6o4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133244/
doi: 10.1016/s0092-8674(88)91285-8
summary:
  Simian virus 5 (SV5), a prototype paramyxovirus, has a single-stranded, negative sense genomic RNA (vRNA) approximately 15,000 nucleotides in chain length that is transcribed in infected cells by the virion-associated RNA transcriptase to yield virus-specific mRNAs. The SV5 "P" gene has been shown to encode both the P protein (Mr = 44,000), and protein V (Mr = 24,000) by the arrest of translation in vitro of both P and V using a cDNA clone derived from SV5-specific mRNAs (Paterson et al., 1984) . Antigenic Region Mapping of the P and V Monoclonal Antibodies on the P and V Gene Using T7 RNA Polymerase Runoff Transcripts, In Vitro Translation, and Immunoprecipitation The full-length P203-1 DNA insert cloned using Xbal linkers (XX) and a Hindlll to Xbal fragment (HX) containing the 3'' two-thirds of the P203-1 DNA were placed under the control of the T7 promoter in the plasmid pGEM-2.

title:
  Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5

abstract:
  The “P≓ gene of the paramyxovirus SV5 encodes two known proteins, P (M(r) ≈ 44,000) and V (M(r) ≈ 24,000). The complete nucleotide sequence of the “P≓ gene has been obtained and is found to contain two open reading frames, neither of which is large enough to encode the P protein. We have shown that the P and V proteins are translated from two mRNAs that differ by the presence of two nontemplated G residues in the P mRNA. These two additional nucleotides convert the two open reading frames to one of 392 amino acids. The P and V proteins are amino coterminal and have 164 amino acids in common. The unique C terminus of V consists of a cysteine-rich region that resembles a cysteine-rich metal binding domain. An open reading frame that contains this cysteine-rich region exists in all other paramyxovirus “P≓ gene sequences examined, which suggests that it may have important biological significance.


id: cord-252433-0e9lonq4
title: Viral RNAs: Lessons from the Enemy
author: Cullen, Bryan R.
date: 2009-02-20
txt: ./txt/cord-252433-0e9lonq4.txt
cache: ./cache/cord-252433-0e9lonq4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.cell.2009.01.048
doi: 10.1016/j.cell.2009.01.048
summary:
  As a result, HIV-1 mutants lacking a functional rev gene are able to express the proteins encoded by fully spliced viral mRNAs, that is, Tat, Nef, and the defective Rev protein itself, but cannot express any of the proteins encoded by incompletely spliced viral mRNAs, including Gag, Pol, and Env. The transcripts encoding these viral structural proteins, however, can be detected in the nucleus of cells infected by Rev-deficient viruses, where they are either degraded or eventually fully spliced and then exported (Cullen, 2003) . MPMV has a simpler genomic organization than HIV-1 and only encodes the three structural proteins Picornaviruses and some flaviviruses Recruits cellular translation factors and ribosomal subunits to viral translation initiation codons in the absence of an mRNA cap Gag, Pol, and Env. Nevertheless, MPMV expresses both a genome-length Gag/ Pol mRNA and a spliced Env mRNA.

abstract:
  Viruses are adept at evolving or co-opting genomic elements that allow them to maximize their replication potential in the infected host. This evolutionary plasticity makes viruses an invaluable system to identify new mechanisms used not only by viruses but also by vertebrate cells to modulate gene expression. Here, I discuss the identification and characterization of viral mRNA structures and noncoding RNAs that have led to important insights into the molecular mechanisms of eukaryotic cells.


id: cord-253259-hmn7mg8j
title: Three-dimensional visualization of the rotavirus hemagglutinin structure
author: Shaw, A. L.
date: 1993-08-27
txt: ./txt/cord-253259-hmn7mg8j.txt
cache: ./cache/cord-253259-hmn7mg8j.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/009286749390516S
doi: 10.1016/0092-8674(93)90516-s
summary:
  Abstract Three-dimensional structures of a native simian and reassortant rotavirus have been determined by electron cryomicroscopy and computer image processing. The structural features of the native virus confirm that the hemagglutinin spike is a dimer of VP4, substantiated by in vivo radiolabeling studies. The difference map between the two structures reveals a novel large globular domain of VP4 buried within the virion that interacts extensively with the intermediate shell protein, VP6. Our results suggest that assembly of VP4 precedes that of VP7, the major outer shell protein, and that VP4 may play an important role in the receptor recognition and budding process through the rough endoplasmic reticulum during virus maturation. Figure 3A shows a surface representation of the The reconstructed density map of SAI 1-4F reveals the complex organization of the outer shell of rotavirus.

abstract:
  Abstract Three-dimensional structures of a native simian and reassortant rotavirus have been determined by electron cryomicroscopy and computer image processing. The structural features of the native virus confirm that the hemagglutinin spike is a dimer of VP4, substantiated by in vivo radiolabeling studies. Exchange of native VP4 with a bovine strain equivalent results in a poorly infectious reassortant. No VP4 spikes are detected in the three-dimensional reconstruction of the reassortant. The difference map between the two structures reveals a novel large globular domain of VP4 buried within the virion that interacts extensively with the intermediate shell protein, VP6. Our results suggest that assembly of VP4 precedes that of VP7, the major outer shell protein, and that VP4 may play an important role in the receptor recognition and budding process through the rough endoplasmic reticulum during virus maturation.


id: cord-253302-keh7s758
title: DNA-Packing Portal and Capsid-Associated Tegument Complexes in the Tumor Herpesvirus KSHV
author: Gong, Danyang
date: 2019-09-05
txt: ./txt/cord-253302-keh7s758.txt
cache: ./cache/cord-253302-keh7s758.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0092867419308347
doi: 10.1016/j.cell.2019.07.035
summary:
  Our atomic models of the portal and capsid/CATC, together with visualization of CATCs'' variable occupancy and alternate orientation of CATC-interacting vertex triplexes, suggest a mechanism whereby the portal orchestrates procapsid formation and asymmetric long-range determination of CATC attachment during DNA packaging prior to pleomorphic tegumentation/envelopment. Unlike the comparatively high occupancies of capsid-associated tegument proteins in alphaherpesviruses Wang et al., 2018) and betaherpesviruses Yu et al., 2017) , KSHV CATC binding sites are markedly partially and/or more flexibly occupied, leading to poorly resolved CATC structures in prior icosahedral reconstructions of KSHV (Dai et al., 2014 . Thus, to accurately assess the specific occupancy of penton vertex CATCs and to understand the structural basis of a CATC''s discriminatory association with portal and penton vertices, we relaxed 5-fold symmetry for penton vertex sub-particles and performed 3D focused classification of their CATC-binding registers ( Figure S1 ).

abstract:
  Assembly of Kaposi’s sarcoma-associated herpesvirus (KSHV) begins at a bacteriophage-like portal complex that nucleates formation of an icosahedral capsid with capsid-associated tegument complexes (CATCs) and facilitates translocation of an ∼150-kb dsDNA genome, followed by acquisition of a pleomorphic tegument and envelope. Because of deviation from icosahedral symmetry, KSHV portal and tegument structures have largely been obscured in previous studies. Using symmetry-relaxed cryo-EM, we determined the in situ structure of the KSHV portal and its interactions with surrounding capsid proteins, CATCs, and the terminal end of KSHV’s dsDNA genome. Our atomic models of the portal and capsid/CATC, together with visualization of CATCs’ variable occupancy and alternate orientation of CATC-interacting vertex triplexes, suggest a mechanism whereby the portal orchestrates procapsid formation and asymmetric long-range determination of CATC attachment during DNA packaging prior to pleomorphic tegumentation/envelopment. Structure-based mutageneses confirm that a triplex deep binding groove for CATCs is a hotspot that holds promise for antiviral development.


id: cord-255856-0xqllbzz
title: O-linked oligosaccharides of mouse egg ZP3 account for its sperm receptor activity
author: Florman, Harvey M.
date: 1985-05-31
txt: ./txt/cord-255856-0xqllbzz.txt
cache: ./cache/cord-255856-0xqllbzz.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/0092867485900844
doi: 10.1016/0092-8674(85)90084-4
summary:
  A specific size class of O-linked oligosaccharides, recovered following mild alkaline hydrolysis and reduction of ZP3, is shown to possess sperm receptor activity and to bind to sperm. In these experiments, a competition assay (Bleil and Wassarman, 1980a; Florman et al., 1984) was used to determine the ability of oligosaccharides, derived from either solubilized zonae pellucidae or purified zona pellucida glycoproteins, to inhibit the binding of sperm to eggs in vitro ("sperm receptor activity"). On the other hand, egg zonae pellucidae subjected to mild alkaline hydrolysis, under the conditions described above, lost approximately 90% of the sperm receptor activity present in untreated samples and in samples treated only with distilled water (Figure 2) . Initial experiments demonstrated that radiolabeled (3H-NaBH,) oligosaccharides, possessing sperm receptor activity, could be recovered from alkaline hydrolysates of egg zonae pellucidae.

abstract:
  Abstract Previously, we reported that ZP3, one of three different glycoproteins present in the mouse egg's zona pellucida, serves as a sperm receptor. Furthermore, small glycopeptides derived from egg ZP3 retain full sperm receptor activity, suggesting a role for carbohydrate, rather than polypeptide chain in receptor function. Here, we report that removal of O-linked oligosaccharides from ZP3 destroys its sperm receptor activity, whereas removal of O-linked oligosaccharides has no effect. A specific size class of O-linked oligosaccharides, recovered following mild alkaline hydrolysis and reduction of ZP3, is shown to possess sperm receptor activity and to bind to sperm. The results presented strongly suggest that mouse sperm bind to eggs via O-linked oligosaccharides present on ZP3.


id: cord-256156-mywhe6w9
title: SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2
author: Clausen, Thomas Mandel
date: 2020-09-14
txt: ./txt/cord-256156-mywhe6w9.txt
cache: ./cache/cord-256156-mywhe6w9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32970989/
doi: 10.1016/j.cell.2020.09.033
summary:
  We show that SARS-CoV-2 spike protein interacts with both cellular heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain (RBD). Unfractionated heparin, non-anticoagulant heparin, heparin lyases, and lung heparan sulfate potently block spike protein binding and/or infection by pseudotyped virus and authentic SARS-CoV-2 virus. In this report, we show that the ectodomain of the SARS-CoV-2 spike (S) protein interacts with cell surface HS through the Receptor Binding Domain (RBD) in the S1 subunit. Adjacent to the ACE2 binding site and exposed in the RBD lies a group of positively-charged amino acid residues that represents a potential site that could interact with heparin or heparan sulfate ( Fig. 1A and Suppl. The SARS-CoV-2 spike protein depends on cellular heparan sulfate for cell binding. Heparin inhibits cellular invasion by SARS-CoV-2: structural dependence of the interaction of the surface protein (spike) S1 receptor binding domain with heparin

abstract:
  We show that SARS-CoV-2 spike protein interacts with both cellular heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain (RBD). Docking studies suggest a heparin/heparan sulfate-binding site adjacent to the ACE2 binding site. Both ACE2 and heparin can bind independently to spike protein in vitro and a ternary complex can be generated using heparin as a scaffold. Electron micrographs of spike protein suggests that heparin enhances the open conformation of the RBD that binds ACE2. On cells, spike protein binding depends on both heparan sulfate and ACE2. Unfractionated heparin, non-anticoagulant heparin, heparin lyases, and lung heparan sulfate potently block spike protein binding and/or infection by pseudotyped virus and authentic SARS-CoV-2 virus. We suggest a model in which viral attachment and infection involves heparan sulfate-dependent enhancement of binding to ACE2. Manipulation of heparan sulfate or inhibition of viral adhesion by exogenous heparin presents new therapeutic opportunities.


id: cord-258372-w0j0n8mn
title: How Support of Early Career Researchers Can Reset Science in the Post-COVID19 World
author: Gibson, Erin M.
date: 2020-06-12
txt: ./txt/cord-258372-w0j0n8mn.txt
cache: ./cache/cord-258372-w0j0n8mn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32533917/
doi: 10.1016/j.cell.2020.05.045
summary:
  Shoring up the foundation of academic science will require a concerted effort between funding agencies, universities, and the public to rethink how we support scientists, with a special emphasis on early career researchers. Shoring up the foundation of academic science will require a concerted effort between funding agencies, universities, and the public to rethink how we support scientists, with a special emphasis on early career researchers. Women, parents, and individuals who identify as racial or ethnic minorities leave science, technology, engineering, and math (STEM) fields as early career researchers at an excessively high rate in the best of times and will undoubtedly suffer more from the present lab closures. Ensuring a Durable Future for Academic Science Post-COVID19 Recovery from the immediate COVID19 crisis necessitates a multi-pronged approach including fiscal and non-fiscal strategies to help graduate students, postdoctoral fellows, and early and later career faculty.

abstract:
  The COVID19 crisis has magnified the issues plaguing academic science, but it has also provided the scientific establishment with an unprecedented opportunity to reset. Shoring up the foundation of academic science will require a concerted effort between funding agencies, universities, and the public to rethink how we support scientists, with a special emphasis on early career researchers.


id: cord-259681-k9cnikqk
title: O-linked oligosaccharides are acquired by herpes simplex virus glycoproteins in the Golgi apparatus
author: Johnson, David C.
date: 1983-03-31
txt: ./txt/cord-259681-k9cnikqk.txt
cache: ./cache/cord-259681-k9cnikqk.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/0092867483900831
doi: 10.1016/0092-8674(83)90083-1
summary:
  These studies were carried out not only under conditions designed to allow normal glycoprotein processing, but also in the presence of monensin, an ionophore known to cause accumulation of secreted and membrane proteins and virions in Golgi-derived vacuoles (Tartakoff and Vassalli, 1978; Uchida et al., 1979; Johnson and Schlesinger, 1980; Johnson and Spear, 1982) , and in ricin-resistant cells defective in the processing of N-linked oligosaccharides. Our results indicate that extension of O-linked oligosaccharides to yield chains of sufficient number or size to affect electrophoretic mobilities of the glycoproteins, and probably also addition of the first amino acid-linked GalNAc residues, occur in the Golgi apparatus subsequent to addition of fatty acid and coincident with the processing of high-mannose-type Nlinked oligosaccharides to complex-type oligosaccharides. The "C-labeled HSVl glycoproteins gC and gD were isolated on preparative SDS-polyacrylamide gels and treated with 0.05 M NaOH, 1 M NaBHa at 45°C for 14-20 hr (mild alkaline borohydride), conditions shown to selectively release O-linked oligosaccharides (Spiro, 1966; Marshall and Neuberger, 1977) .

abstract:
  Abstract The O-linked oligosaccharides on mature forms of herpes simplex virus type 1 (HSV1) glycoproteins were characterized, and were found to account largely for the lower electrophoretic mobilities of these forms relative to the mobilities of immature forms. Other posttranslational modifications of HSV1 glycoproteins (designated gB, gC, gD and gE) were related temporally to the discrete shifts in electrophoretic mobilities that signal acquisition of the O-linked oligosaccharides. Fatty acid acylation (principally of gE) could be detected just prior to the shifts, whereas conversion of high-mannosetype N-linked oligosaccharides to the complex type occurred coincident with the shifts. The addition of O-linked oligosaccharides did not occur in cells treated with the ionophore monensin or in a ricinresistant cell line defective in the processing of N-linked oligosaccharides. We conclude that extension of O-linked oligosaccharide chains on HSV1 glycoproteins, and probably also attachment of the first O-linked sugars, occurs as a late posttranslational modification in the Golgi apparatus.


id: cord-263468-996kl9jz
author: Cattaneo, Roberto
date: 1988-10-21
txt: ./txt/cord-263468-996kl9jz.txt
cache: ./cache/cord-263468-996kl9jz.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/0092867488900487
doi: 10.1016/0092-8674(88)90048-7
summary:
  Abstract We assessed the alterations of viral gene expression occurring during persistent infections by cloning full-length transcripts of measles virus (MV) genes from brain autopsies of two subacute sclerosing panencephalitis patients and one measles inclusion body encephalitis (MIBE) patient. One of these nucleotide substitutions and one deletion resulted in alteration of the reading frames of two fusion genes, as confirmed by in vitro translation of synthetic mRNAs. One cluster of mutations was exceptional; in the matrix gene of the MIBE case, 50% of the U residues were changed to C, which might result from a highly biased copying event exclusively affecting this gene. most likely based on one hand on the low fidelity of RNA To assess the variability in strains of lytic viruses, and replication (Domingo et al., 1978; for review see Steinto estimate the number of mutations introduced during hauer and Holland, 1987) and on the other hand on the persistence, we counted the differences of lytic and perlow selective pressure exerted on viral genomes in nonsistent viruses from a consensus as defined above.

title:
  Biased hypermutation and other genetic changes in defective measles viruses in human brain infections

abstract:
  Abstract We assessed the alterations of viral gene expression occurring during persistent infections by cloning full-length transcripts of measles virus (MV) genes from brain autopsies of two subacute sclerosing panencephalitis patients and one measles inclusion body encephalitis (MIBE) patient. The suquence of these MV genes revealed that, most likely, almost 2% of the nucleotides were mutated during persistence, and 35% of these differences resulted in amino acid changes. One of these nucleotide substitutions and one deletion resulted in alteration of the reading frames of two fusion genes, as confirmed by in vitro translation of synthetic mRNAs. One cluster of mutations was exceptional; in the matrix gene of the MIBE case, 50% of the U residues were changed to C, which might result from a highly biased copying event exclusively affecting this gene. We propose that the cluster of mutations in the MIBE case, and other combinations of mutations in other cases, favored propagation of MV infections in brain cells by conferring a selective advantage to the mutated genomes.


id: cord-266480-u8o4eitu
title: Preventing outbreaks through interactive, experiential real-life simulations
author: Colubri, Andrés
date: 2020-09-02
txt: ./txt/cord-266480-u8o4eitu.txt
cache: ./cache/cord-266480-u8o4eitu.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32905783/
doi: 10.1016/j.cell.2020.08.042
summary:
  Operation Outbreak (OO) is an educational curriculum and simulation platform that uses Bluetooth to spread a virtual "pathogen" in real-time across smartphones in close proximity. The app-generated data from these simulations represented the "ground truth" of the mock outbreaks, captured several essential features of SARS-CoV-2, and allowed us to observe behavioral changes among participants--many of which are now being mirrored in real life. Our 2018 SMA Ebola simulation first showed how student social-distancing could affect an "outbreak''s" trajectory ( Figure 2A More detailed data from the 2019 simulation allowed us to reconstruct transmission chains over time and identify important features of the outbreak, such as the existence of two super-spreaders causing 4 and 5 secondary infections early in the game ( Figure 2C ). We envision OO as playing two key roles: (1) as a pedagogical platform for teaching fundamentals of pandemic response that are vital for the public to understand and (2) as a novel system for simulating outbreaks and evaluating real-world mitigation strategies, including those needed to restart in-person education.

abstract:
  Operation Outbreak (OO) is a simulation platform that teaches students how pathogens spread and the impact of interventions, thereby facilitating the safe re-opening of schools. In addition, OO generates data to inform epidemiological models and prevent future outbreaks. Before SARS-CoV-2 was reported we repeatedly simulated a virus with similar features, correctly predicting many human behaviors later observed during the pandemic.


id: cord-267046-ewnjgps5
title: Virus Evolution: How Does an Enveloped Virus Make a Regular Structure?
author: Strauss, James H
date: 2001-04-06
txt: ./txt/cord-267046-ewnjgps5.txt
cache: ./cache/cord-267046-ewnjgps5.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0092867401002914
doi: 10.1016/s0092-8674(01)00291-4
abstract: nan
summary:
  key: cord-267046-ewnjgps5 title: Virus Evolution: How Does an Enveloped Virus Make a Regular Structure? cord_uid: ewnjgps5 They propose a fit of E1 into the cryo-75 residues long, of which about 38 residues are present EM density of Semliki Forest virus determined to 9 Å in the ectodomain. The paper by Pletnev ture flavivirion containing prM (about 170 residues) et al. The Evolution of Enveloped Viruses E2 projects upward to the full-length of the spike. Thus, The parallels between the assembly of alphaviruses and E1 forms what has been called the skirt that surrounds flaviviruses and the similarities in structure revealed by the lipid bilayer and part of the lower domains of the the present studies suggest that an enveloped virus spikes, whereas E2 forms the projecting part of the with an icosahedral structure arose long ago and has spike. viruses whose structures are more or less known use quite different assembly mechanisms ( Virus evolution


id: cord-269023-g21a9ik2
title: Before Virus, After Virus: A Reckoning
author: Mukherjee, Siddhartha
date: 2020-10-15
txt: ./txt/cord-269023-g21a9ik2.txt
cache: ./cache/cord-269023-g21a9ik2.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33064987/
doi: 10.1016/j.cell.2020.09.042
summary:
  When he transferred these active lymphocytes-later found to be B cells-from an antigen-exposed animal to a naive animal (an ingeniously simple experiment), Gowans found that he could transfer antibody-mediated immunity as well. In a paper published in Nature, Michel Nussenzweig and his colleagues dissected the immune response to SARS-CoV-2 infection (Robbiani et al., 2020) . The sustained activation of certain patterns of chemokines and cytokines was correlated with severe illness-a phenomenon that Iwasaki has termed ''''immunological misfiring.'''' A more recent paper, published in Cell, also implicated dysfunctions in innate immune cells, particularly myeloid cells such as neutrophils and monocytes, in patients with severe COVID infection (Schulte-Schrepping et al., 2020) . ''''If you mount a robust innate immune response during the early phase of infection, you control the virus and have a mild disease.

abstract:
  The 2020 Lasker Awards, a celebration of one of the most prestigious international prizes given to individuals for extraordinary contributions to Basic and Clinical Medical Research, Pubic Health, and Special Achievement, was cancelled because of the COVID-19 pandemic. Typically, essays on the awardees and their scientific and medical contributions are solicited and published in Cell in collaboration with the Lasker Committee. This year, the Lasker Committee commissioned an essay to reflect on the historic contributions that scientists and physicians have made to our understanding of immunology and virology, and future directions in medical and basic research that have been highlighted by COVID-19 pandemic.


id: cord-270082-byxd4o4m
title: Identification of essential components of the S. cerevisiae kinetochore
author: Doheny, Kimberly Floy
date: 1993-05-21
txt: ./txt/cord-270082-byxd4o4m.txt
cache: ./cache/cord-270082-byxd4o4m.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/8500169/
doi: 10.1016/0092-8674(93)90255-o
summary:
  Readthrough Assay and Secondary Screen of the ctf Collection When transcription from a strong promoter is initiated toward a CEN DNA sequence, the mitotic segregational function of the centromere is destroyed (Hill and Bloom, 1987) without disruption of its 180-220 bp nuclease protected region (Bloom et al., 1984; Hill and Bloom, 1987) , indicating that at least some of the kinetochore complex remains intact. To test the hypothesis that a CfN DNA-protein complex was responsible for the transcriptional block, we replaced the wild-type CENG sequence with a CEN6 sequence containing a single-nucleotide point mutation (CDEIII-15C) in the central element of the palindrome of CDEIII (CCG). Of 34 cff mutants screened (see Experimental Procedures for list), 7 were identified as putative kinetochore mutants because they produced an intermediate level of blue colony color between the levels of the CTF+ strains carrying the wild-type and mutant CEN reporters.

abstract:
  Abstract We have designed and utilized two in vivo assays of kinetochore integrity in S. cerevisiae. One assay detects relaxation of a transcription block formed at centromeres; the other detects an increase in the mitotic stability of a dicentric test chromosome. ctf13-30 and ctf14-42 were identified as putative kinetochore mutants by both assays. CTF14 is identical to NDC10 CBF2 , a recently identified essential gene that encodes a 110 kd kinetochore component. CTF13 is an essential gene that encodes a predicted 478 amino acid protein with no homology to known proteins. ctf13 mutants missegregate chromosomes at permissive temperature and transiently arrest at nonpermissive temperature as large-budded cells with a G2 DNA content and a short spindle. Antibodies recognizing epitope-tagged CTF13 protein decrease the electrophoretic mobility of a CEN DNA-protein complex formed in vitro. Together, the genetic and biochemical data indicate that CTF13 is an essential kinetochore protein.


id: cord-271032-imc6woht
title: Severe COVID-19 is marked by a dysregulated myeloid cell compartment
author: Schulte-Schrepping, Jonas
date: 2020-08-05
url: https://doi.org/10.1016/j.cell.2020.08.001
doi: 10.1016/j.cell.2020.08.001
abstract:
  Summary Coronavirus Disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progresses to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19, associated with increased neutrophil counts and dysregulated immune responses, remains unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole blood and peripheral blood mononuclear cells to determine changes in immune cell composition and activation in mild vs. severe COVID-19 (242 samples from 109 individuals) over time. HLA-DRhiCD11chi inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DRlo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.


id: cord-272520-7mci4mip
title: Identification of an ER retrieval signal in a retroviral glycoprotein
author: Goepfert, P. A.
date: 1995-08-25
txt: ./txt/cord-272520-7mci4mip.txt
cache: ./cache/cord-272520-7mci4mip.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/7664333/
doi: 10.1016/0092-8674(95)90026-8
abstract: nan
summary:
  To mediate budding of infectious viral particles through intracellular membranes, viral glycoproteins must fulfill two requirements: a signal for sorting to an intracellular compartment and an interaction with the core proteins of the virus. Similar to certain classic oncoviruses, the foamy viruses utilize a B/D-type virus assembly strategy by which immature viral capsids assemble in the cytoplasm in advance of virion budding (Achong et al., 1971; Hooks and Gibbs, 1975) . We hypothesized that foamy virus glycoproteins must possess a specific signal for sorting to an intracellular compartment of the secretory pathway. Remarkably, we identified the dilysine ER retrieval signal at the cytoplasmic carboxyl termini of four of the five available foamy virus glycoprotein sequences ( Table 2 ). If the glycoprotein cytoplasmic tails interact with preassembled viral capsids, which may localize to the same intracellular site, coordinated budding of glycoprotein-bearing infectious virus particles into an early post-ER compartment results.


id: cord-279463-bli8hwda
author: Lipp, Joachim
date: 1986-09-26
txt: ./txt/cord-279463-bli8hwda.txt
cache: ./cache/cord-279463-bli8hwda.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/3530500/
doi: 10.1016/0092-8674(86)90710-5
summary:
  As type II membrane proteins contain only a single stretch of hydrophobic amino acid residues, this might function as a signal for membrane insertion as well as a membrane anchor (Markoff et al., 1984; Spiess and Lodish, 1986) . plycat is an in-frame fusion between the 5'' region of ly encoding the cytoplas, mic, membrane-spanning segment plus 12 amino acids of the exoplasmic portion of ly and the gene encoding the cytoplasmic protein chloramphenicol acetyltransferase (CAT). After protease digestion in the presence of microsomal membranes, lyCAT* is reduced in molecular weight by about 2 kd, suggesting that it exposes 20-30 amino acid residues on the cytoplasmic side ( Figure 3 , lanes 2 and 3). This signal sequence is located in the amino-terminal half of the membrane-spanning segment, and it is cleaved when the preceding cytoplasmic domain is removed.

title:
  The membrane-spanning segment of invariant chain (Iγ) contains a potentially cleavable signal sequence

abstract:
  Abstract The human invariant chain (Iγ) of class II histocompatibility antigens spans the membrane of the endoplasmic reticulum once. It exposes a small amino-terminal domain on the cytoplasmic side and a carboxyterminal, glycosylated domain on the exoplasmic side of the membrane. When the exoplasmic domain of Iγ is replaced by the cytoplasmic protein chloramphenicol acetyltransferase (CAT), CAT becomes the exoplasmic, glycosylated domain of the resulting membrane protein IγCAT∗. Deletion of the hydrophilic cytoplasmic domain from IγCAT gives rise to a secreted protein from which an amino-terminal segment is cleaved, most likely by signal peptidase. We conclude that the membrane-spanning region of Iγ contains a signal sequence in its amino-terminal half and that hydrophilic residues at the amino-terminal end of a signal sequence can determine cleavage by signal peptidase.


id: cord-284609-1q75zw6b
title: Recombination in RNA
author: King, Andrew M.Q.
date: 1982-07-31
url: https://api.elsevier.com/content/article/pii/0092867482904548
doi: 10.1016/0092-8674(82)90454-8
abstract:
  Abstract The aphthovirus genome consists of a single molecule of single-stranded RNA that encodes all the virus-induced proteins. We isolated recombinant aphthoviruses from cells simultaneously infected with temperature-sensitive mutants of two different subtype strains. Analysis of the proteins induced by 16 independently generated recombinants revealed two types of protein pattern, which were consistent with single genetic crossovers on the 5′ side and 3′ side, respectively, of the central P34-coding region. Recombinants invariably inherited all four coat proteins from the same parent, and novel recombinant proteins were not observed. RNAase T1 fingerprints of virus RNA, prepared from representatives of each recombinant type, confirmed the approximate crossover sites that had been deduced from the inheritance of proteins. These fingerprints provide molecular evidence of recombination at the level of RNA and demonstrate the potential of RNA recombination for producing genetic diversity among picornaviruses.


id: cord-284944-hcgfe9wv
title: Elevated calprotectin and abnormal myeloid cell subsets discriminate severe from mild COVID-19
author: Silvin, Aymeric
date: 2020-08-05
txt: ./txt/cord-284944-hcgfe9wv.txt
cache: ./cache/cord-284944-hcgfe9wv.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0092867420309934?v=s5
doi: 10.1016/j.cell.2020.08.002
summary:
  Thus, we performed high dimensional flow cytometry and single cell RNA sequencing of COVID-19 patient peripheral blood cells and detected the disappearance of non-classical CD14LowCD16High monocytes, the accumulation of HLA-DRLow classical monocytes, and the release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Validating these discovery experiments, we performed mass cytometry analysis of an independent cohort of 12 patients (four in each group; control, mild and severe) ( Table S5) , which showed a lower fraction of CD14 Low CD16 High non-classical monocytes in severe compared to mild patients ( Figure 3F and 3G ). This study presents evidence that patients who develop a severe COVID-19 exhibit high levels of calprotectin and inflammatory cytokines and chemokines correlating with an emergency myelopoiesis generating ROS-and NOS-expressing immunosuppressive myeloid cells (HLA-DR Low monocytes and immature subsets of neutrophils).

abstract:
  Summary Blood myeloid cells are known to be dysregulated in the coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2. It is unknown whether the innate myeloid response differs with disease severity, and whether markers of innate immunity discriminate high risk patients. Thus, we performed high dimensional flow cytometry and single cell RNA sequencing of COVID-19 patient peripheral blood cells and detected the disappearance of non-classical CD14LowCD16High monocytes, the accumulation of HLA-DRLow classical monocytes, and the release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Immature CD10LowCD101-CXCR4+/- neutrophils with an immuno-suppressive profile accumulated as well in blood and lungs, suggesting emergency myelopoiesis. We finally showed that calprotectin plasma level and a routine flow cytometry assay detecting decreased frequencies of non-classical monocytes could discriminate patients who develop a severe COVID-19 form, suggesting a predictive value that deserves prospective evaluation.


id: cord-287349-1zcq7kzx
author: Chen, James
date: 2020-07-28
txt: ./txt/cord-287349-1zcq7kzx.txt
cache: ./cache/cord-287349-1zcq7kzx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32783916/
doi: 10.1016/j.cell.2020.07.033
summary:
  title: Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex Here we present cryo-electron microscopic structures of the SARS-CoV-2 holo-RdRp with an RNA template-product in complex with two molecules of the nsp13 helicase. The structure places the nucleic acid-binding ATPase domains of the helicase directly in front of the replicating-transcribing holo-RdRp, constraining models for nsp13 function. The analogous structural 234 arrangement leads us to propose that the SARS-CoV-2 RdRp may backtrack, generating a single-235 stranded RNA segment at the 3''-end that would extrude out the RdRp secondary channel 236 Table S1 ; Video S1). This aspect of helicase function could provide the NTP-296 dependent motor activity necessary to backtrack the RdRp. In cellular organisms, DdRp 297 backtracking plays important roles in many processes, including the control of pausing during 298 transcription elongation, termination, DNA repair, and fidelity (Nudler, 2012) . Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase

title:
  Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex

abstract:
  Summary SARS-CoV-2 is the causative agent of the 2019-2020 pandemic. The SARS-CoV-2 genome is replicated and transcribed by the RNA-dependent RNA polymerase holoenzyme (subunits nsp7/nsp82/nsp12) along with a cast of accessory factors. One of these factors is the nsp13 helicase. Both the holo-RdRp and nsp13 are essential for viral replication and are targets for treating the disease COVID-19. Here we present cryo-electron microscopic structures of the SARS-CoV-2 holo-RdRp with an RNA template-product in complex with two molecules of the nsp13 helicase. The Nidovirus-order-specific N-terminal domains of each nsp13 interact with the N-terminal extension of each copy of nsp8. One nsp13 also contacts the nsp12-thumb. The structure places the nucleic acid-binding ATPase domains of the helicase directly in front of the replicating-transcribing holo-RdRp, constraining models for nsp13 function. We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapeutic development.


id: cord-287815-alv30uk5
title: The Golgi complex: In vitro veritas?
author: Mellman, Ira
date: 1992-03-06
txt: ./txt/cord-287815-alv30uk5.txt
cache: ./cache/cord-287815-alv30uk5.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/009286749290027A
doi: 10.1016/0092-8674(92)90027-a
abstract: nan
summary:
  As we have seen, there are three key elements underlying our general view of the Golgi: that the Golgi consists of several discrete compartments (cis, medial, trans, and TGN) corresponding to individual or groups of cisternae; that transit between these compartments occurs viavesicular carriers; and that the transport process is inherently nonselective with respect to the passenger proteins. While distinct from the CGN or TGN, we assume that the medial cisternae represent a single functionally continuous compartment, irrespective of the actual number of physically separate cisternal elements in any one Golgi complex. Given that VSV G protein in early Golgi compartments was transported with the highest efficiency (Fries and Rothman, 1981) the transport event assayed was postulated to reflect the formation of vesicles from cis (early) cisternae and the fusion of these vesicles with medial cisternae (which contain the GlcNAc transferase) (Rothman and Orci, 1990) (Figure 4) .


id: cord-289765-79cmcvfi
title: How to Boost the Impact of Scientific Conferences
author: Morrison, Mike
date: 2020-09-03
url: https://www.sciencedirect.com/science/article/pii/S0092867420309375
doi: 10.1016/j.cell.2020.07.029
abstract:
  We can maximize the impact of scientific conferences by uploading all conference presentations, posters, and abstracts to highly trafficked public repositories for each content type. Talks can be hosted on sites like YouTube and Youku, posters can be published on Figshare, and papers and abstracts can become open access preprints.


id: cord-291790-z5rwznmv
title: The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity
author: Li, Qianqian
date: 2020-07-17
url: https://www.sciencedirect.com/science/article/pii/S0092867420308771?v=s5
doi: 10.1016/j.cell.2020.07.012
abstract:
  Summary The spike protein of SARS-CoV-2 has been undergoing mutations and is highly glycosylated. It is critically important to investigate the biological significance of these mutations. Here we investigated 80 variants and 26 glycosylation site modifications for the infectivity and reactivity to a panel of neutralizing antibodies and sera from convalescent patients. D614G, along with several variants containing both D614G and another amino acid change, were significantly more infectious. Most variants with amino acid change at receptor binding domain were less infectious but variants including A475V, L452R, V483A and F490L became resistant to some neutralizing antibodies. Moreover, the majority of glycosylation deletions were less infectious whilst deletion of both N331 and N343 glycosylation drastically reduced infectivity, revealing the importance of glycosylation for viral infectivity. Interestingly, N234Q was markedly resistant to neutralizing antibodies, whereas N165Q became more sensitive. These findings could be of value in the development of vaccine and therapeutic antibodies.


id: cord-294429-isivkz8b
author: Grifoni, Alba
date: 2020-05-20
url: https://www.ncbi.nlm.nih.gov/pubmed/32473127/
doi: 10.1016/j.cell.2020.05.015
title:
  Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals

abstract:
  Summary Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide ‘megapools’, circulating SARS-CoV-2−specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2−reactive CD4+ T cells in ∼40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS-CoV-2.


id: cord-295062-8rl4kswe
title: Virus Entry: Open Sesame
author: Marsh, Mark
date: 2006-02-24
txt: ./txt/cord-295062-8rl4kswe.txt
cache: ./cache/cord-295062-8rl4kswe.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0092867406001826
doi: 10.1016/j.cell.2006.02.007
summary:
  Virus Particles as Devices for Targeted Gene Transfer A viral particle is composed of nucleic acids (RNA or DNA), protein, and, in the case of enveloped viruses, membrane lipids. Viruses use signaling activities to induce changes in the cell that promote viral entry and early cytoplasmic events, as well as to optimize later processes in the replication cycle. Like cholera toxin, these viruses bind to the sugar moiety of gangliosides and enter cells via caveolar/raft pathways that are dependent on cholesterol ( Figures 2D and 2E ) and the activation of tyrosine-kinase signaling cascades (Anderson et al., 1996; Pelkmans et al., 2001; Smith et al., 2003a; Stang et al., 1997; Tsai et al., 2003) . Nevertheless, in the majority of cases, the transfer of viral genomes from cell to cell appears to occur through the formation of virus particles that are released from infected cells and use the mechanisms described above to enter new uninfected hosts.

abstract:
  Detailed information about the replication cycle of viruses and their interactions with host organisms is required to develop strategies to stop them. Cell biology studies, live-cell imaging, and systems biology have started to illuminate the multiple and subtly different pathways that animal viruses use to enter host cells. These insights are revolutionizing our understanding of endocytosis and the movement of vesicles within cells. In addition, such insights reveal new targets for attacking viruses before they can usurp the host-cell machinery for replication.


id: cord-295894-us5x1jtg
title: SnapShot: FABP Functions
author: Li, Bing
date: 2020-08-20
txt: ./txt/cord-295894-us5x1jtg.txt
cache: ./cache/cord-295894-us5x1jtg.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0092867420309351
doi: 10.1016/j.cell.2020.07.027
summary:
  Abbreviations: FABPs, fatty acid binding proteins; NFκB: nuclear factor kappa B; COX2, cyclooxygenase-2; CER, ceramide; LXR, liver X receptor; PGE2, prostaglandin E2; SCD1, stearoyl-CoA desaturase 1; STAT, signal transducer and activator of transcription; LTA4, leukotriene A4; RAR, retinoic acid receptor; NLRP3, nucleotide-binding domain leucine-rich repeat and pyrin domain containing 3; ASC, apoptosis-associated speck-like protein containing a caspase-recruitment domain; IFNβ, interferon β; LTB4, leukotriene B4; HSL, hormone sensitive lipase; PPAR, peroxisome proliferator-activated receptors; DIO2, deiodinase type 2; β-AR, β-adrenergic receptor; ALDH1, aldehyde dehydrogenase isoform 1; PCK1, phosphoenolpyruvate carboxykinase 1. Generally, FABPs function as cytoplasmic lipid chaperones to (1) facilitate fatty acid solubilization, trafficking, and metabolism; (2) interact with various membrane and intracellular proteins (e.g., peroxisome proliferator-activated receptors [PPARs] , hormone sensitive lipase [HSL]); and (3) regulate tissue and cellular specific lipid responses (middle wheel panel). In summary, accumulating evidence has demonstrated that FABP members not only exert overlapping functions in lipid binding and transport but exhibit unique characteristics in specific cells and tissues as well. Expression of Adipocyte/Macrophage Fatty Acid-Binding Protein in Tumor-Associated Macrophages Promotes Breast Cancer Progression

abstract:
  Fatty acid binding proteins (FABPs) serve as intracellular chaperones for fatty acids and other hydrophobic ligands inside cells. Recent studies have demonstrated new functions of individual members of the FABP family. This Snapshot describes the overall functions of FABPs in health and disease and highlights emerging roles of adipose FABP (A-FABP) and epidermal FABP (E-FABP) in the fields of obesity, chronic inflammation, and cancer development. To view this SnapShot, open or download the PDF.


id: cord-301997-63160t7f
author: Schwer, Beate
date: 1987-07-17
url: https://www.ncbi.nlm.nih.gov/pubmed/3594569/
doi: 10.1016/0092-8674(87)90212-1
title:
  Discontinuous transcription or RNA processing of vaccinia virus late messengers results in a 5′ poly(A) leader

abstract:
  Abstract We have demonstrated by primer elongation and cap analysis that mature vaccinia virus late transcripts are discontinuously synthesized. We have shown that RNA transcripts from a translocated 11K and from the authentic 11K and 4b late promoters are extended by approximately 35 nucleotides beyond the “start site” determined by S1 mapping using vaccinia genomic DNA as a probe. Sequencing of the RNA and of the first strand cDNA reveal that a homopolymeric poly(A) sequence is linked to the 5′ terminus of the RNA transcripts. S1 mapping of RNA transcripts with a DNA probe containing an A-stretch, replacing promoter sequences upstream of position −1, confirms the existence of a poly(A) leader of approximately 35 A-residues.


id: cord-302020-ypsh3rjv
title: The Architecture of SARS-CoV-2 Transcriptome
author: Kim, Dongwan
date: 2020-04-23
txt: ./txt/cord-302020-ypsh3rjv.txt
cache: ./cache/cord-302020-ypsh3rjv.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32330414/
doi: 10.1016/j.cell.2020.04.011
summary:
  In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2. (A) Read counts from nanopore direct RNA sequencing of total RNA from Vero cells infected with SARS-CoV-2. We further discovered RNA modification sites and measured the poly(A) tail length of gRNAs and sgRNAs. To delineate the SARS-CoV-2 transcriptome, we first performed DRS runs on a MinION nanopore sequencer with total RNA extracted from Vero cells infected with SARS-CoV-2 (Be-taCoV/Korea/KCDC03/2020). To unambiguously investigate the modifications, we generated negative control RNAs by in vitro transcription of the viral sequences and performed a DRS run on these unmodified controls ( Figure S4A ).

abstract:
  SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Although the SARS-CoV-2 genome was reported recently, its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous discontinuous transcription events. In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif, AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the modification and the 3′ tail. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.


id: cord-305173-95o5z685
title: A TRIFfic Perspective on Acute Lung Injury
author: Martin, Thomas R.
date: 2008-04-18
txt: ./txt/cord-305173-95o5z685.txt
cache: ./cache/cord-305173-95o5z685.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0092867408004546
doi: 10.1016/j.cell.2008.04.006
summary:
  In the complex inflammatory response initiated by HCl in the lungs, one might expect that TLR4 would be activated by several different endogenous stimuli; however, mice lacking TLR4, TRIF, or TRAF6 all resisted HClas well as OxPAPC-induced inflammation, supporting a role for OxPAPC as an important stimulus of TLR4 activation in this model. As in the HCl injury model, immunohistochemical analysis identified OxPAPC in the lungs, but mice lacking TLR4 or TRIF had lung inflammation that was much less severe. Mice lacking the Ncf1 protein, which lack an active NADPH oxidase complex, were protected from viral lung inflammation and did not form OxPAPC in the airspaces, further supporting a key role for oxidation of phospholipids in the pathogenic pathway. OxPAPC activates TLR4 expressed by myeloid cells (an alveolar macrophage is shown), and the intracellular signal is transduced by the adaptor proteins TRIF and TRAF6, leading to interleukin 6 (IL-6) production, inflammation, and alveolar damage.

abstract:
  Acute lung injury (ALI) is a leading cause of death in people infected with H5N1 avian influenza virus or the SARS-coronavirus. Imai et al. (2008) now report that ALI is triggered by the signaling of oxidized phospholipids through Toll-like receptor 4 (TLR4) and the adaptor protein TRIF. These findings provide insight into the molecular pathogenesis of ALI, a condition for which treatment options are currently very limited.


id: cord-305290-xnjwv0d7
title: Ribosome gymnastics—Degree of difficulty 9.5, style 10.0
author: Atkins, John F.
date: 1990-08-10
txt: ./txt/cord-305290-xnjwv0d7.txt
cache: ./cache/cord-305290-xnjwv0d7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/2199062/
doi: 10.1016/0092-8674(90)90007-2
abstract: nan
summary:
  A single base change in the mouse mammary tumor virus (MMTV) gag-pro shift site, from the normal A AAA AAC to A AAA AAG, surprisingly leads from ~2% to 50% -1 frameshifting at this sequence (a 25-fold increase); and the lo-fold decrease between A AAA AAG and A AAA AAA affords an interesting glimpse at how the nuances of codon-anticodon interaction can govern the efficiency of this type of shifting. These results should be interpreted with caution, as all the higher eukaryotic frameshifting studies with altered sequences have been done with a reticulocyte lysate cell-free translation system; there are likely to be differences in the number of ribosomes loaded per message, and perhaps in the tRNA balance, from less specialized cells in vivo.


id: cord-307021-uppekume
author: Crooke, Elliott
date: 1988-09-23
txt: ./txt/cord-307021-uppekume.txt
cache: ./cache/cord-307021-uppekume.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/0092867488901158
doi: 10.1016/0092-8674(88)90115-8
summary:
  Pro-OmpA preincubated at 21°C with membrane vesicles lost competence for subsequent membrane translocation ( Figure 6 , lane 11) while preincubation in the presence of membranes and trigger factor, but without ATP and NADH (lane 12), stabilized the assembly-active precursor. SRP Stabilizes ProOmpA for Membrane Translocation Like trigger factor, canine SRP ha8 been shown to recognize presecretory proteins, although until now its activity has been assayed in the context of a polysome. Nikko1 does not inhibit the membrane assembly of proOmpA that has already formed a complex with trigger factor (Figure 9 , lane 3, no detergent; lane 4, detergent added), and thus has no effect on the membrane translocation "machinery" per se or on the protease protection assay. It is likely that other soluble proteins, such as those encoded by the secA and se& genes, would bind to our preparations of plasma membrane vesicles or, if added to the in vitro translocation in the absence (lane 2) or presence (lanes 3 and 4) of trigger factor (100 ng).

title:
  ProOmpA is stabilized for membrane translocation by either purified E. coli trigger factor or canine signal recognition particle

abstract:
  Abstract We have isolated large amounts of E. coli outer-membrane protein A precursor (proOmpA). Purified proOmpA is active in membrane assembly, and this assembly is saturable with respect to the precursor protein. A proOmpA-Sepharose matrix allows affinity isolation of trigger factor, a soluble, 63,000 dalton monomeric protein that stabilizes proOmpA in assembly competent form. Comparison of trigger factor's amino-terminal sequence with those in a computer data bank and with those encoded by sec genes, as well as groEL and heat shock gene dnaK, suggests that trigger factor is encoded by a previously undescribed gene. Trigger factor and proOmpA form a 1:1 complex that can be isolated by gel filtration. Purified canine signal recognition particle (SRP) can also stabilize proOmpA for membrane insertion. This post-ribosomal activity of SRP suggests a unifying theme in protein translocation mechanisms.


id: cord-312115-foy3dsq4
title: Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19
author: Sekine, Takuya
date: 2020-08-14
txt: ./txt/cord-312115-foy3dsq4.txt
cache: ./cache/cord-312115-foy3dsq4.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0092867420310084?v=s5
doi: 10.1016/j.cell.2020.08.017
summary:
  In line with these data, we found that CD8 + T cells specific for cytomegalovirus (CMV) or Epstein-Barr virus (EBV) more commonly expressed CD38, but not HLA-DR, Ki-67, or PD-1, in patients with acute moderate or severe COVID-19 compared with convalescent individuals and healthy blood donors, indicating limited bystander activation and proliferation during the early phase of infection with SARS-CoV-2 ( Figure 2A , B and Figure S3C ). On the basis of these observations, we quantified functional SARS-CoV-2-specific memory T cell responses across five distinct cohorts, including healthy individuals who donated blood either before or during the pandemic, family members who shared a household with convalescent individuals and were exposed at the time of symptomatic disease, and individuals in the convalescent phase after mild or severe COVID-19. These donors exhibited robust memory T cell responses months after infection, even in the absence of detectable circulating antibodies specific for SARS-CoV-2, indicating a previously unanticipated degree of population-level immunity against COVID-19.

abstract:
  Summary SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We here systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust, broad and highly functional memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.


id: cord-318276-so5jooj0
title: Vaccinia virus produces late mRNAs by discontinuous synthesis
author: Bertholet, Christine
date: 1987-07-17
txt: ./txt/cord-318276-so5jooj0.txt
cache: ./cache/cord-318276-so5jooj0.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/009286748790211X
doi: 10.1016/0092-8674(87)90211-x
summary:
  RNA was isolated from noninfected or infected cells and then hybridized to 32P-labeled probes isolated from the 5'' end region, upstream of the 11K coding sequences of cDNA clones 3, 8, and 9 (see Figure 2 ). To confirm this, and to identify the regions from which they are transcribed, the cDNA-derived probes used in the previous experiment were hybridized to cloned DNA restriction fragments representing the entire vaccinia virus genome ( Figure 4 ). %P-labeled DNA probes (~3, ~9, p9, pllK) derived from the 5'' region of the corresponding cDNA clones or from genomic DNA (see Figure 2 ) were hybridized lo RNA isolated from uninfected (HeLa) or infected (Early, Late) cells, or to tRNA immobilized on a nitrocellulose membrane. Total late RNA from infected cells protected fragments of 127 and 128 nucleotides of the genomic probe, consistent with the previous experiments, which demonstrated that the sequence complementarity between the genomic DNA and 11K mRNA ends just upstream of the 11K ATG codon.

abstract:
  Abstract We describe the unusual structure of a vaccinia virus late mRNA. In these molecules, the protein-coding sequences of a major late structural polypeptide are preceded by long leader RNAs, which in some cases are thousands of nucleotides long. These sequences map to different regions of the viral genome and in one instance are separated from the late gene by more than 100 kb of DNA. Moreover, the leader sequences map either upstream or downstream of the late gene, are transcribed from either DNA strand, and are fused to the late gene coding sequence via a poly(A) stretch. This demonstrates that vaccinia virus produces late mRNAs by tagging the protein-coding sequences onto the 3′ end of other RNAs.


id: cord-321308-rwxhdg8r
title: Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear
author: Grubaugh, Nathan D.
date: 2020-07-03
txt: ./txt/cord-321308-rwxhdg8r.txt
cache: ./cache/cord-321308-rwxhdg8r.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0092867420308175
doi: 10.1016/j.cell.2020.06.040
summary:
  While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown. Following the emergence of SARS-CoV-2 in China in late 2019, and the rapid expansion of the COVID-19 pandemic in 2020, questions about viral evolution have come tumbling after. They present compelling data that an amino acid change in the virus'' spike protein, D614G, emerged early during the pandemic, and viruses containing G614 are now dominant in many places around the world. In support of their hypothesis, the authors provided evidence that clinical samples from G614 infections have a higher levels of viral RNA, and produced higher titers in pseudoviruses from in vitro experiments; results that now seem to be corroborated by others [e.g. Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus Naturally mutated spike proteins of SARS-CoV-2 variants show differential levels of cell entry

abstract:
  Abstract Korber et al. (2020) found that a SARS-CoV-2 variant in the spike protein, D614G, rapidly became dominant around the world. While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.


id: cord-321868-xk4yuibj
author: Belcourt, Michael F.
date: 1990-07-27
txt: ./txt/cord-321868-xk4yuibj.txt
cache: ./cache/cord-321868-xk4yuibj.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/009286749090371K
doi: 10.1016/0092-8674(90)90371-k
summary:
  Our tRNA overproduction data suggest that a leucyl-tRNA, probably tRNALeu UAG, an unusual leucine isoacceptor that recognizes all six leucine codons, slips from CUU-Leu onto UUA-Leu (in the +1 reading frame) during a translational pause at the AGG-Arg codon induced by the low availability of tRNAArg CCU, encoded by a single-copy essential gene. In these systems, a simultaneous slippage of tRNAs in the A and P sites of the translating ribosome on the homopolymeric sequence results in a frameshift to the pro orpol reading frame and suppression of the gag frame termination codon. The 14 nucleotide frameshift site has a Gln residue (rather than His) following Gly. The amino acid sequence through the 14 nucleotide site confirms the Gln residue after Gly (data not shown), supporting the notion that translation shifts to the +l reading frame by peptidyl-tRNA slippage on the CUU-Leu codon.

title:
  Ribosomal frameshifting in the yeast retrotransposon Ty: tRNAs induce slippage on a 7 nucleotide minimal site

abstract:
  Abstract Ribosomal frameshifting regulates expression of the TYB gene of yeast Ty retrotransposons. We previously demonstrated that a 14 nucleotide sequence conserved between two families of Ty elements was necessary and sufficient to support ribosomal frameshifting. This work demonstrates that only 7 of these 14 nucleotides are needed for normal levels of frameshifting. Any change to the sequence CUU-AGG-C drastically reduces frameshifting; this suggests that two specific tRNAs, tRNALeu UAG and tRNAArg CCU, are involved in the event. Our tRNA overproduction data suggest that a leucyl-tRNA, probably tRNALeu UAG, an unusual leucine isoacceptor that recognizes all six leucine codons, slips from CUU-Leu onto UUA-Leu (in the +1 reading frame) during a translational pause at the AGG-Arg codon induced by the low availability of tRNAArg CCU, encoded by a single-copy essential gene. Frameshifting is also directional and reading frame specific. Interestingly, frameshifting is inhibited when the “slip” CUU codon is located three codons downstream, but not four or more codons downstream, of the translational initiation codon.


id: cord-326916-bakwk4tm
title: Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States
author: Fauver, Joseph R.
date: 2020-05-07
url: https://doi.org/10.1016/j.cell.2020.04.021
doi: 10.1016/j.cell.2020.04.021
abstract:
  The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.


id: cord-327349-rxb6zfoc
title: Cancer, COVID-19, and antiviral immunity: the CAPTURE study
author: Au, Lewis
date: 2020-09-03
txt: ./txt/cord-327349-rxb6zfoc.txt
cache: ./cache/cord-327349-rxb6zfoc.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0092867420311466
doi: 10.1016/j.cell.2020.09.005
summary:
  Inherent perturbations on cell subsets (e.g. lymphoid and myeloid malignancies), or therapy-induced impact on immune states (e.g. immune checkpoint blockade) may provide opportunities to understand contributions of distinct immune compartments and key regulators of the anti-SARS-CoV-2 response. Herein, we aim to provide an overview of knowledge to-date of the clinical features of COVID-19 observed in cancer patients, as well as potential impact of cancer and anti-cancer interventions on the immune response to SARS-CoV-2. However, what has been critically missing in cohort and registry reports to date are data on 1) the true prevalence of SARS-CoV-2 infection in the cancer population, given population screening has not been widely implemented; and 2) the experience of those who remain well (uninfected, asymptomatic or subclinically affected), to determine the drivers of mortality and the absolute risks of severe adverse events within the cancer community as a whole. A longitudinal understanding of the degree to which the immunocompromised states of cancer patients impact infection, viral clearance, clinical course of COVID-19, and subsequent generation of long-term immunity is needed.

abstract:
  The SARS-CoV-2 pandemic has posed a significant challenge for risk evaluation and mitigation amongst cancer patients. Susceptibility to and severity of COVID-19 in cancer patients has not been studied in a prospective and broadly applicable manner. CAPTURE is a pan-cancer, longitudinal immune profiling study designed to address this knowledge gap.


id: cord-328289-3h3kmjlz
title: Effects of COVID-19 on the nervous system
author: Iadecola, Costantino
date: 2020-08-19
txt: ./txt/cord-328289-3h3kmjlz.txt
cache: ./cache/cord-328289-3h3kmjlz.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0092867420310709
doi: 10.1016/j.cell.2020.08.028
summary:
  Another Parkinson''s disease patient with obesity, hypertension and diabetes, exhibited at autopsy, in addition to hypoxic-ischemic neuronal damage, microhemorrhages, white matter lesions and enlarged perivascular spaces, but no evidence of SARS-CoV-2 in the brain (Kantonen et al., 2020) . The encephalopathy is most likely a consequence of systemic factors, such as cytokine sickness, hypoxia and metabolic dysfunction due to peripheral organ failure, while the strokes seem to be related more to hypercoagulability and endothelial injury than to SARS-CoV-2 vasculitis affecting brain vessels. In some cases, the possibility of a SARS-CoV-2 encephalitis could not be ruled out based on the potential for the virus to infect neurons (Song et al., 2020) , but definitive clinical and pathological evidence of neurotropism is lacking.

abstract:
  Summary Neurological complications have emerged as a significant cause of morbidity and mortality in the ongoing COVID-19 pandemic. Beside respiratory insufficiency, many hospitalized patients exhibit neurological manifestations, ranging from headache and loss of smell, to confusion and disabling strokes. COVID-19 is also anticipated to take a toll on the nervous system in the long term. Here we will provide a critical appraisal of the potential for neurotropism and mechanisms of neuropathogenesis of SARS-CoV-2, as they relate to the acute and chronic neurological consequences of the infection. Finally, we will examine potential avenues for future research and therapeutic development.


id: cord-334123-wb45ww7f
title: RNA pseudoknots that interact with components of the translation apparatus
author: Schimmel, Paul
date: 1989-07-14
txt: ./txt/cord-334123-wb45ww7f.txt
cache: ./cache/cord-334123-wb45ww7f.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/2473840/
doi: 10.1016/0092-8674(89)90395-4
abstract: nan
summary:
  A third and earlier study proposed that an RNA pseudoknot is recognized by a DNA binding protein that autogenously regulates translation of its mRNA (McPheeters et al., 1988) . The tRNA-like structures at the 3'' ends of plant viral RNAs provide one example where the pseudoknot format may be necessary to form a substrate that is specifically recognized by an enzyme. Previous structural mapping experiments by Draper and co-workers suggested a model for the 5'' region of the mRNA which constitutes the S4 binding site; it envisions a hairpin helix and loop that encompasses nucleotides 19 to 72. The second study provides evidence that pseudoknot formation in a viral mRNA is required for frameshift suppression of a termination codon that, in turn, allows a fusion protein to be synthesized from two overlapping reading frames. This element encodes a stem-loop structure that starts six nucleotides downstream from the proposed site of frameshifting, near the end of the first reading frame.


id: cord-336696-c3rbmysh
title: SnapShot: COVID-19
author: Oberfeld, Blake
date: 2020-04-30
url: https://doi.org/10.1016/j.cell.2020.04.013
doi: 10.1016/j.cell.2020.04.013
abstract:
  Abstract Coronavirus disease 2019 (COVID-19) is a novel respiratory illness caused by SARS-CoV-2. Viral entry is mediated through viral spike protein and host ACE2 enzyme interaction. Most cases are mild; severe disease often involves cytokine storm and organ failure. Therapeutics including antivirals, immunomodulators, and vaccines are in development. To view this SnapShot, open or download the PDF.


id: cord-339093-mwxkvwaz
title: High potency of a bivalent human VH domain in SARS-CoV-2 animal models
author: Li, Wei
date: 2020-09-04
txt: ./txt/cord-339093-mwxkvwaz.txt
cache: ./cache/cord-339093-mwxkvwaz.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S009286742031148X
doi: 10.1016/j.cell.2020.09.007
summary:
  It potently neutralized mouse adapted SARS-CoV-2 in wild type mice at a dose as low as 2 mg/kg and exhibited high prophylactic and therapeutic efficacy in a hamster model of SARS-CoV-2 infection, possibly enhanced by its relatively small size. To identify potent neutralizing V H s against SARS-CoV-2, we panned our large (10 11 clones) and diverse phage-displayed human V H antibody library against recombinant RBD. One of those V H s, ab8, in an Fc (human IgG1, crystallizable fragment) fusion format, showed potent neutralization activity and specificity against SARS-CoV-2 both in vitro and in two animal models. They also suggest that the double mutations Q498T/P499Y on RBD did not influence V H -Fc ab8 binding and contribute to the validation of the mouse adapted SARS-CoV-2 model for evaluation of neutralizing antibody efficacy. In conclusion, we identified a fully human antibody V H domain that shows strong competition with ACE2 for binding to RBD and potent neutralization of SARS-CoV-2 in vitro and in two animal models.

abstract:
  Novel COVID-19 therapeutics are urgently needed. We generated a phage-displayed human antibody VH domain library from which we identified a high-affinity VH binder ab8. Bivalent VH, VH-Fc ab8 bound with high avidity to membrane-associated S glycoprotein and to mutants found in patients. It potently neutralized mouse adapted SARS-CoV-2 in wild type mice at a dose as low as 2 mg/kg and exhibited high prophylactic and therapeutic efficacy in a hamster model of SARS-CoV-2 infection, possibly enhanced by its relatively small size. Electron microscopy combined with scanning mutagenesis identified ab8 interactions with all three S protomers and showed how ab8 neutralized the virus by directly interfering with ACE2 binding. VH-Fc ab8 did not aggregate and did not bind to 5300 human membrane-associated proteins. The potent neutralization activity of VH-Fc ab8 combined with good developability properties and cross-reactivity to SARS-CoV-2 mutants provide a strong rationale for its evaluation as a COVID-19 therapeutic.


id: cord-342189-ya05m58o
title: SARS-CoV-2 disrupts splicing, translation, and protein trafficking to suppress host defenses
author: Banerjee, Abhik K.
date: 2020-10-08
txt: ./txt/cord-342189-ya05m58o.txt
cache: ./cache/cord-342189-ya05m58o.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0092867420313106
doi: 10.1016/j.cell.2020.10.004
summary:
  Here, we comprehensively define the interactions between each SARS-CoV-2 protein and human RNAs. We show that 10 viral proteins form highly specific interactions with mRNAs or ncRNAs, including those involved in progressive steps of host cell protein production. We show J o u r n a l P r e -p r o o f 5 that NSP16 binds to the mRNA recognition domains of the U1 and U2 RNA components of the spliceosome and acts to suppress global mRNA splicing in SARS-CoV-2-infected human cells. We identified several pathogenic functions of SARS-CoV-2 in human cells -including global inhibition of host mRNA splicing, protein translation, and membrane protein trafficking -and described the molecular mechanisms by which the virus acts to disrupt these essential cell processes.

abstract:
  SARS-CoV-2 is a recently identified coronavirus that causes the respiratory disease known as COVID-19. Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis. Here, we comprehensively define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the Signal Recognition Particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses.


id: cord-345103-b2wkm03g
title: Molecular architecture of the SARS-CoV-2 virus
author: Yao, Hangping
date: 2020-09-06
url: https://www.ncbi.nlm.nih.gov/pubmed/32979942/
doi: 10.1016/j.cell.2020.09.018
abstract:
  SARS-CoV-2 is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins, detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryo-electron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in both pre- and postfusion conformations were determined to average resolutions of 8.7-11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass-spectrometry, which revealed highly similar overall processing states of the native glycans to that of the recombinant glycoprotein glycans. The native conformation of the ribonucleoproteins (RNP) and its higher-order assemblies were revealed. Overall, these characterizations have revealed the architecture of the SARS-CoV-2 virus in exceptional detail, and shed lights on how the virus packs its ∼30 kb long single-segmented RNA in the ∼80 nm diameter lumen.


id: cord-350855-gofzhff7
title: SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract
author: Hou, Yixuan J.
date: 2020-05-27
txt: ./txt/cord-350855-gofzhff7.txt
cache: ./cache/cord-350855-gofzhff7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.cell.2020.05.042
doi: 10.1016/j.cell.2020.05.042
summary:
  High-sensitivity RNA in situ mapping revealed the highest ACE2 expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) vs distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. We measured the relative infectivity of the SARS-CoV-2 GFP virus in primary 283 cells based on the average peak titers and observed that infectivity exhibited the same 284 pattern as the ACE2 expression levels from the upper to lower respiratory tract ( Figure 285 6Bi-6Biv). Gene 1230 expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human 1231 airway epithelial cells and lung tissue

abstract:
  Summary The mode of acquisition and causes for the variable clinical spectrum of COVID-19 remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore SARS-CoV-2 pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest ACE2 expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) vs distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.


