Accessory proteins of SARS-CoV and other coronaviruses

Abstract The huge RNA genome of SARS coronavirus comprises a number of open reading frames that code for a total of eight accessory proteins. Although none of these are essential for virus replication, some appear to have a role in virus pathogenesis. Notably, some SARS-CoV accessory proteins have been shown to modulate the interferon signaling pathways and the production of pro-inflammatory cytokines. The structural information on these proteins is also limited, with only two (p7a and p9b) having their structures determined by X-ray crystallography. This review makes an attempt to summarize the published knowledge on SARS-CoV accessory proteins, with an emphasis on their involvement in virus–host interaction. The accessory proteins of other coronaviruses are also briefly discussed. This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10years of research on highly pathogenic human coronaviruses” (see Introduction by Hilgenfeld and Peiris (2013)).

[1]  W. Lu,et al.  Severe acute respiratory syndrome coronavirus accessory protein 9b is a virion-associated protein , 2009, Virology.

[2]  P. Rottier,et al.  Live, Attenuated Coronavirus Vaccines through the Directed Deletion of Group-Specific Genes Provide Protection against Feline Infectious Peritonitis , 2004, Journal of Virology.

[3]  Shengqi Wang,et al.  Subcellular localization and membrane association of SARS-CoV 3a protein , 2005, Virus Research.

[4]  Jincun Zhao,et al.  The N-Terminal Region of Severe Acute Respiratory Syndrome Coronavirus Protein 6 Induces Membrane Rearrangement and Enhances Virus Replication , 2010, Journal of Virology.

[5]  Stuart G. Siddell,et al.  A Contemporary View of Coronavirus Transcription , 2006, Journal of Virology.

[6]  M. Lenardo,et al.  Molecular Determinants for Subcellular Localization of the Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame 3b Protein , 2009, Journal of Virology.

[7]  R. Baric,et al.  SARS Coronavirus 3 b Accessory Protein Modulates Transcriptional Activity of RUNX 1 b , 2011 .

[8]  Y. Leo,et al.  Profiles of Antibody Responses against Severe Acute Respiratory Syndrome Coronavirus Recombinant Proteins and Their Potential Use as Diagnostic Markers , 2004, Clinical Diagnostic Laboratory Immunology.

[9]  W. Hong,et al.  Understanding the accessory viral proteins unique to the severe acute respiratory syndrome (SARS) coronavirus , 2006, Antiviral Research.

[10]  W. Hong,et al.  Characterization of a Unique Group-Specific Protein (U122) of the Severe Acute Respiratory Syndrome Coronavirus , 2004, Journal of Virology.

[11]  S. Inglis,et al.  Association of the infectious bronchitis virus 3c protein with the virion envelope , 1991, Virology.

[12]  P. Britton,et al.  Gene 5 of the Avian Coronavirus Infectious Bronchitis Virus Is Not Essential for Replication , 2005, Journal of Virology.

[13]  W. Hong,et al.  The Severe Acute Respiratory Syndrome Coronavirus 3a Protein Up-Regulates Expression of Fibrinogen in Lung Epithelial Cells , 2005, Journal of Virology.

[14]  S. Perlman,et al.  Pathogenicity of severe acute respiratory coronavirus deletion mutants in hACE-2 transgenic mice , 2008, Virology.

[15]  S. Inglis,et al.  Identification of two new polypeptides encoded by mRNA5 of the coronavirus infectious bronchitis virus , 1992, Virology.

[16]  F. Taguchi.  [SARS coronavirus]. , 2003, Uirusu.

[17]  P. Halbur,et al.  Pathogenicity and sequence analysis studies suggest potential role of gene 3 in virulence of swine enteric and respiratory coronaviruses. , 1997, Advances in experimental medicine and biology.

[18]  S. Perlman,et al.  Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Coronavirus Infections , 2006, Journal of Virology.

[19]  R. D. de Groot,et al.  Glycosylation of the Severe Acute Respiratory Syndrome Coronavirus Triple-Spanning Membrane Proteins 3a and M , 2006, Journal of Virology.

[20]  F. Fischer,et al.  The internal open reading frame within the nucleocapsid gene of mouse hepatitis virus encodes a structural protein that is not essential for viral replication , 1997, Journal of virology.

[21]  H. Nauwynck,et al.  ORF7-encoded accessory protein 7a of feline infectious peritonitis virus as a counteragent against IFN-α-induced antiviral response. , 2014, The Journal of general virology.

[22]  M. Lai,et al.  The 8ab protein of SARS-CoV is a luminal ER membrane-associated protein and induces the activation of ATF6 , 2009, Virology.

[23]  E. Huizinga,et al.  The Murine Coronavirus Hemagglutinin-esterase Receptor-binding Site: A Major Shift in Ligand Specificity through Modest Changes in Architecture , 2012, PLoS pathogens.

[24]  Jincun Zhao,et al.  Severe Acute Respiratory Syndrome Coronavirus Protein 6 Is Required for Optimal Replication , 2008, Journal of Virology.

[25]  S. Shen,et al.  Emergence of a coronavirus infectious bronchitis virus mutant with a truncated 3b gene: functional characterization of the 3b protein in pathogenesis and replication , 2003, Virology.

[26]  W. Hong,et al.  A Novel Severe Acute Respiratory Syndrome Coronavirus Protein, U274, Is Transported to the Cell Surface and Undergoes Endocytosis , 2004, Journal of Virology.

[27]  Zu-feng Guo,et al.  Amino terminus of the SARS coronavirus protein 3a elicits strong, potentially protective humoral responses in infected patients. , 2006, The Journal of general virology.

[28]  P. Mcgeer,et al.  SARS corona virus peptides recognized by antibodies in the sera of convalescent cases , 2004, Virology.

[29]  S. Inglis,et al.  Internal entry of ribosomes on a tricistronic mRNA encoded by infectious bronchitis virus , 1992, Journal of virology.

[30]  S. Inglis,et al.  A polycistronic mRNA specified by the coronavirus infectious bronchitis virus , 1991, Virology.

[31]  J. Lenstra,et al.  Predicted membrane topology of the coronavirus protein E1. , 1986, Biochemistry.

[32]  Yang Yang,et al.  The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists , 2013, Protein & Cell.

[33]  C. Hopkins,et al.  Signal-dependent membrane protein trafficking in the endocytic pathway. , 1993, Annual review of cell biology.

[34]  J. Epstein,et al.  Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor , 2013, Nature.

[35]  Kouji Matsushima,et al.  Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF‐κB activation , 2006, FEBS Letters.

[36]  Z. Ye,et al.  A SARS-CoV protein, ORF-6, induces caspase-3 mediated, ER stress and JNK-dependent apoptosis , 2008, Biochimica et Biophysica Acta (BBA) - General Subjects.

[37]  Xuming Zhang,et al.  The hemagglutinin/esterase gene of human coronavirus strain OC43: Phylogenetic relationships to bovine and murine coronaviruses and influenza C virus☆ , 1992, Virology.

[38]  P. Palese,et al.  Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame (ORF) 3b, ORF 6, and Nucleocapsid Proteins Function as Interferon Antagonists , 2006, Journal of Virology.

[39]  Krishna Shankara Narayanan,et al.  Severe Acute Respiratory Syndrome Coronavirus 3a Protein Is Released in Membranous Structures from 3a Protein-Expressing Cells and Infected Cells , 2006, Journal of Virology.

[40]  Andreas Pichlmair,et al.  Inhibition of Beta Interferon Induction by Severe Acute Respiratory Syndrome Coronavirus Suggests a Two-Step Model for Activation of Interferon Regulatory Factor 3 , 2005, Journal of Virology.

[41]  M. Waye,et al.  Expression and functional characterization of the putative protein 8b of the severe acute respiratory syndrome‐associated coronavirus , 2006, FEBS Letters.

[42]  S. Perlman,et al.  A Severe Acute Respiratory Syndrome-Associated Coronavirus-Specific Protein Enhances Virulence of an Attenuated Murine Coronavirus , 2005, Journal of Virology.

[43]  J. Lippincott-Schwartz,et al.  The Open Reading Frame 3a Protein of Severe Acute Respiratory Syndrome-Associated Coronavirus Promotes Membrane Rearrangement and Cell Death , 2009, Journal of Virology.

[44]  Faizan Ahmad,et al.  The SARS Coronavirus 3a Protein Causes Endoplasmic Reticulum Stress and Induces Ligand-Independent Downregulation of the Type 1 Interferon Receptor , 2009, PloS one.

[45]  Andrew Pekosz,et al.  Structure and Intracellular Targeting of the SARS-Coronavirus Orf7a Accessory Protein , 2005, Structure.

[46]  S. Perlman,et al.  Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Hepatitis Virus Infections by More than One Mechanism , 2008, Journal of Virology.

[47]  J. Armstrong,et al.  Assembly in vitro of a spanning membrane protein of the endoplasmic reticulum: the E1 glycoprotein of coronavirus mouse hepatitis virus A59. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[48]  R. Silverman,et al.  Homologous 2′,5′-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity , 2013, Proceedings of the National Academy of Sciences.

[49]  R. Silverman,et al.  Antagonism of the Interferon-Induced OAS-RNase L Pathway by Murine Coronavirus ns2 Protein Is Required for Virus Replication and Liver Pathology , 2012, Cell Host & Microbe.

[50]  W. Fischer,et al.  Assembly of Viral Membrane Proteins. , 2009, Journal of chemical theory and computation.

[51]  Matthias Stoldt,et al.  Solution structure of the X4 protein coded by the SARS related coronavirus reveals an immunoglobulin like fold and suggests a binding activity to integrin I domains , 2005, Journal of biomedical science.

[52]  D. Labie,et al.  Molecular Evolution , 1991, Nature.

[53]  Krystal L. Matthews,et al.  The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling. , 2014, The Journal of general virology.

[54]  T. Gallagher,et al.  SARS-coronavirus protein 6 conformations required to impede protein import into the nucleus , 2010, Virus Research.

[55]  R. Silverman,et al.  Cell-Type-Specific Activation of the Oligoadenylate Synthetase–RNase L Pathway by a Murine Coronavirus , 2013, Journal of Virology.

[56]  J. Timoney,et al.  Feline infectious peritonitis. , 1976, The Veterinary clinics of North America.

[57]  Yonggang Liu,et al.  Civets Are Equally Susceptible to Experimental Infection by Two Different Severe Acute Respiratory Syndrome Coronavirus Isolates , 2005, Journal of Virology.

[58]  V. Chow,et al.  The 3a accessory protein of SARS coronavirus specifically interacts with the 5'UTR of its genomic RNA, Using a unique 75 amino acid interaction domain. , 2007, Biochemistry.

[59]  Alexander E Gorbalenya,et al.  Mechanisms and enzymes involved in SARS coronavirus genome expression. , 2003, The Journal of general virology.

[60]  H. Goossens,et al.  The first complete genome sequences of clinical isolates of human coronavirus 229E , 2012, Virus Genes.

[61]  B. Hogue,et al.  The 9-kDa hydrophobic protein encoded at the 3′ end of the porcine transmissible gastroenteritis coronavirus genome is membrane-associated , 1992, Virology.

[62]  W. Balch,et al.  A di-acidic signal required for selective export from the endoplasmic reticulum. , 1997, Science.

[63]  Yee-Joo Tan,et al.  The Severe Acute Respiratory Syndrome (SARS)-coronavirus 3a protein may function as a modulator of the trafficking properties of the spike protein , 2005, Virology Journal.

[64]  L. Babiuk,et al.  Intracellular localization of the SARS coronavirus protein 9b: Evidence of active export from the nucleus , 2007, Virus Research.

[65]  A. Mirazimi,et al.  A putative diacidic motif in the SARS-CoV ORF6 protein influences its subcellular localization and suppression of expression of co-transfected expression constructs , 2011, BMC Research Notes.

[66]  J. Bonifacino,et al.  Signals for sorting of transmembrane proteins to endosomes and lysosomes. , 2003, Annual review of biochemistry.

[67]  E. Calvo,et al.  Severe acute respiratory syndrome coronavirus accessory proteins 6 and 9b interact in vivo , 2012, Virus Research.

[68]  Marie-Christine Brun,et al.  TreeDyn: towards dynamic graphics and annotations for analyses of trees , 2006, BMC Bioinformatics.

[69]  Julian Druce,et al.  Induction of Apoptosis by the Severe Acute Respiratory Syndrome Coronavirus 7a Protein Is Dependent on Its Interaction with the Bcl-XL Protein , 2007, Journal of Virology.

[70]  P. Masters,et al.  The Molecular Biology of Coronaviruses , 2006, Advances in Virus Research.

[71]  N. Van Rooijen,et al.  Cell-Type-Specific Type I Interferon Antagonism Influences Organ Tropism of Murine Coronavirus , 2011, Journal of Virology.

[72]  S. Booth,et al.  SARS-CoV 9b Protein Diffuses into Nucleus, Undergoes Active Crm1 Mediated Nucleocytoplasmic Export and Triggers Apoptosis When Retained in the Nucleus , 2011, PloS one.

[73]  Krishna Shankara Narayanan,et al.  Severe Acute Respiratory Syndrome Coronavirus 3a Protein Is a Viral Structural Protein , 2005, Journal of Virology.

[74]  Abraham J Koster,et al.  SARS-Coronavirus Replication Is Supported by a Reticulovesicular Network of Modified Endoplasmic Reticulum , 2008, PLoS biology.

[75]  Z. Yao,et al.  SARS coronavirus 7 a protein blocks cell cycle progression at G 0 / G 1 phase via the cyclin D 3 / pRb pathway , 2006 .

[76]  Andrew Pekosz,et al.  The ORF7b Protein of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Is Expressed in Virus-Infected Cells and Incorporated into SARS-CoV Particles , 2006, Journal of Virology.

[77]  B. Berkhout,et al.  Human coronavirus 229E encodes a single ORF4 protein between the spike and the envelope genes , 2006, Virology Journal.

[78]  P. Woo,et al.  Coexistence of Different Genotypes in the Same Bat and Serological Characterization of Rousettus Bat Coronavirus HKU9 Belonging to a Novel Betacoronavirus Subgroup , 2010, Journal of Virology.

[79]  W. Hong,et al.  The severe acute respiratory syndrome coronavirus 3a is a novel structural protein , 2005, Biochemical and Biophysical Research Communications.

[80]  T. Fung,et al.  Upregulation of CHOP/GADD153 during Coronavirus Infectious Bronchitis Virus Infection Modulates Apoptosis by Restricting Activation of the Extracellular Signal-Regulated Kinase Pathway , 2013, Journal of Virology.

[81]  Ralph S. Baric,et al.  Severe Acute Respiratory Syndrome Coronavirus ORF6 Antagonizes STAT1 Function by Sequestering Nuclear Import Factors on the Rough Endoplasmic Reticulum/Golgi Membrane , 2007, Journal of Virology.

[82]  Guoping Zhao,et al.  Molecular Evolution of the SARS Coronavirus During the Course of the SARS Epidemic in China , 2004, Science.

[83]  Erik L. L. Sonnhammer,et al.  Kalign – an accurate and fast multiple sequence alignment algorithm , 2005, BMC Bioinformatics.

[84]  H. Nauwynck,et al.  The role of accessory proteins in the replication of feline infectious peritonitis virus in peripheral blood monocytes , 2012, Veterinary Microbiology.

[85]  Y. Wang,et al.  Characterization of the 3a Protein of SARS-associated Coronavirus in Infected Vero E6 Cells and SARS Patients , 2004, Journal of Molecular Biology.

[86]  E. Huizinga,et al.  Structure of coronavirus hemagglutinin-esterase offers insight into corona and influenza virus evolution , 2008, Proceedings of the National Academy of Sciences.

[87]  X. L. Liu,et al.  Isolation and Characterization of Viruses Related to the SARS Coronavirus from Animals in Southern China , 2003, Science.

[88]  P. Woo,et al.  Comparative Analysis of Twelve Genomes of Three Novel Group 2c and Group 2d Coronaviruses Reveals Unique Group and Subgroup Features , 2006, Journal of Virology.

[89]  Andrew Pekosz,et al.  The Transmembrane Domain of the Severe Acute Respiratory Syndrome Coronavirus ORF7b Protein Is Necessary and Sufficient for Its Retention in the Golgi Complex , 2008, Journal of Virology.

[90]  P. Britton,et al.  Identification of a Noncanonically Transcribed Subgenomic mRNA of Infectious Bronchitis Virus and Other Gammacoronaviruses , 2012, Journal of Virology.

[91]  H. Geuze,et al.  Coronavirus M proteins accumulate in the Golgi complex beyond the site of virion budding , 1994, Journal of virology.

[92]  J. Maniloff,et al.  Virus taxonomy : eighth report of the International Committee on Taxonomy of Viruses , 2005 .

[93]  David I. Stuart,et al.  The Crystal Structure of ORF-9b, a Lipid Binding Protein from the SARS Coronavirus , 2006, Structure.

[94]  P. Palese,et al.  The E3 protein of bovine coronavirus is a receptor-destroying enzyme with acetylesterase activity , 1988, Journal of virology.

[95]  M. Waye,et al.  The putative protein 6 of the severe acute respiratory syndrome‐associated coronavirus: Expression and functional characterization , 2005, FEBS Letters.

[96]  D. Willbold,et al.  Assembling an ion channel: ORF 3a from SARS‐CoV , 2013, Biopolymers.

[97]  Raja Mazumder,et al.  Detection of novel members, structure–function analysis and evolutionary classification of the 2H phosphoesterase superfamily , 2002, Nucleic acids research.

[98]  M. Peiris,et al.  From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses , 2013, Antiviral Research.

[99]  Christian Drosten,et al.  Characterization of a Novel Coronavirus Associated with Severe Acute Respiratory Syndrome , 2003, Science.

[100]  S. Makino,et al.  Severe Acute Respiratory Syndrome Coronavirus 7a Accessory Protein Is a Viral Structural Protein , 2006, Journal of Virology.

[101]  Sheng Ye,et al.  Atomic structure of a Na+- and K+-conducting channel , 2006, Nature.

[102]  Caroline C. Friedel,et al.  Analysis of Intraviral Protein-Protein Interactions of the SARS Coronavirus ORFeome , 2007, PloS one.

[103]  Jianyong Li,et al.  Mitochondrial location of severe acute respiratory syndrome coronavirus 3b protein. , 2006, Molecules and cells.

[104]  W. Hong,et al.  Overexpression of 7a, a Protein Specifically Encoded by the Severe Acute Respiratory Syndrome Coronavirus, Induces Apoptosis via a Caspase-Dependent Pathway , 2004, Journal of Virology.

[105]  K. Strebel,et al.  The HIV-1 Vpu protein: a multifunctional enhancer of viral particle release. , 2003, Microbes and infection.

[106]  Jiapei Chen,et al.  G0/G1 arrest and apoptosis induced by SARS-CoV 3b protein in transfected cells , 2005, Virology Journal.

[107]  C. Peters,et al.  Severe Acute Respiratory Syndrome Coronavirus Accessory Protein 6 Is a Virion-Associated Protein and Is Released from 6 Protein-Expressing Cells , 2007, Journal of Virology.

[108]  G. Browning,et al.  Infectious Bronchitis Viruses with a Novel Genomic Organization , 2007, Journal of Virology.

[109]  V. Ditt,et al.  Reverse genetic characterization of the natural genomic deletion in SARS-Coronavirus strain Frankfurt-1 open reading frame 7b reveals an attenuating function of the 7b protein in-vitro and in-vivo , 2009, Virology Journal.

[110]  Hanzhong Wang,et al.  Humoral and Cellular Immune Responses Induced by 3a DNA Vaccines against Severe Acute Respiratory Syndrome (SARS) or SARS-Like Coronavirus in Mice , 2008, Clinical and Vaccine Immunology.

[111]  D. Willbold,et al.  SARS-CoV accessory protein 7a directly interacts with human LFA-1 , 2007, Biological chemistry.

[112]  R. Silverman.  Viral Encounters with 2′,5′-Oligoadenylate Synthetase and RNase L during the Interferon Antiviral Response , 2007, Journal of Virology.

[113]  P. Rottier,et al.  The 29-Nucleotide Deletion Present in Human but Not in Animal Severe Acute Respiratory Syndrome Coronaviruses Disrupts the Functional Expression of Open Reading Frame 8 , 2007, Journal of Virology.

[114]  S. Perlman,et al.  Enhancement of Murine Coronavirus Replication by Severe Acute Respiratory Syndrome Coronavirus Protein 6 Requires the N-Terminal Hydrophobic Region but Not C-Terminal Sorting Motifs , 2007, Journal of Virology.

[115]  N. Zhong,et al.  The protein X4 of severe acute respiratory syndrome-associated coronavirus is expressed on both virus-infected cells and lung tissue of severe acute respiratory syndrome patients and inhibits growth of Balb/c 3T3 cell line. , 2005, Chinese medical journal.

[116]  F. Tay,et al.  Expression, post‐translational modification and biochemical characterization of proteins encoded by subgenomic mRNA8 of the severe acute respiratory syndrome coronavirus , 2007, The FEBS journal.

[117]  Wei Lu,et al.  Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release , 2006, Proceedings of the National Academy of Sciences.

[118]  Shuyi Zhang,et al.  Full-length genome sequences of two SARS-like coronaviruses in horseshoe bats and genetic variation analysis. , 2006, The Journal of general virology.

[119]  S. Jameel,et al.  Severe acute respiratory syndrome coronavirus 3a protein activates the mitochondrial death pathway through p38 MAP kinase activation. , 2008, The Journal of general virology.

[120]  Guo-Ping Zhao,et al.  Tracing SARS-Coronavirus Variant with Large Genomic Deletion , 2005, Emerging infectious diseases.

[121]  Y. Guan,et al.  Unique and Conserved Features of Genome and Proteome of SARS-coronavirus, an Early Split-off From the Coronavirus Group 2 Lineage , 2003, Journal of Molecular Biology.

[122]  Yusen Zhou,et al.  G1 phase cell cycle arrest induced by SARS-CoV 3a protein via the cyclin D3/pRb pathway. , 2007, American journal of respiratory cell and molecular biology.

[123]  R. Baric,et al.  Severe Acute Respiratory Syndrome Coronavirus Group-Specific Open Reading Frames Encode Nonessential Functions for Replication in Cell Cultures and Mice , 2005, Journal of Virology.

[124]  Y. Guan,et al.  The severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[125]  Chi-Hung Lin,et al.  Open Reading Frame 8a of the Human Severe Acute Respiratory Syndrome Coronavirus Not Only Promotes Viral Replication but Also Induces Apoptosis , 2007, The Journal of infectious diseases.

[126]  A. Danchin,et al.  The Severe Acute Respiratory Syndrome , 2003 .

[127]  Alexander E. Gorbalenya,et al.  Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans , 2012, mBio.

[128]  Sek-Man Wong,et al.  Identification of Hepta- and Octo-Uridine stretches as sole signals for programmed +1 and −1 ribosomal frameshifting during translation of SARS-CoV ORF 3a variants , 2006, Nucleic acids research.

[129]  Z. Yao,et al.  SARS coronavirus 7a protein blocks cell cycle progression at G0/G1 phase via the cyclin D3/pRb pathway , 2005, Virology.

[130]  J. Sung,et al.  The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells. , 2005, The Journal of general virology.

[131]  Susanna K. P. Lau,et al.  Coronavirus Genomics and Bioinformatics Analysis , 2010, Viruses.

[132]  R. Baric,et al.  SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b , 2012, PloS one.

[133]  K. Yuen,et al.  Middle East Respiratory Syndrome Coronavirus 4a Protein Is a Double-Stranded RNA-Binding Protein That Suppresses PACT-Induced Activation of RIG-I and MDA5 in the Innate Antiviral Response , 2014, Journal of Virology.

[134]  Kwok-Hung Chan,et al.  Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[135]  Juan Carlos Oliveros,et al.  Alphacoronavirus Protein 7 Modulates Host Innate Immune Response , 2013, Journal of Virology.

[136]  Krishna Shankara Narayanan,et al.  SARS coronavirus accessory proteins , 2007, Virus Research.

[137]  Obi L. Griffith,et al.  The Genome Sequence of the SARS-Associated Coronavirus , 2003, Science.

[138]  A. Pekosz,et al.  Severe Acute Respiratory Syndrome Coronavirus Gene 7 Products Contribute to Virus-Induced Apoptosis , 2007, Journal of Virology.

[139]  S. Tsui,et al.  The ion channel activity of the SARS-coronavirus 3a protein is linked to its pro-apoptotic function , 2009, The International Journal of Biochemistry & Cell Biology.

[140]  A. McGoldrick,et al.  Characterisation of a recent virulent transmissible gastroenteritis virus from Britain with a deleted ORF 3a , 2014, Archives of Virology.

[141]  Wanjin Hong,et al.  Severe acute respiratory syndrome coronavirus protein 7a interacts with hSGT , 2006, Biochemical and Biophysical Research Communications.

[142]  T. Hodgson,et al.  Neither the RNA nor the Proteins of Open Reading Frames 3a and 3b of the Coronavirus Infectious Bronchitis Virus Are Essential for Replication , 2006, Journal of Virology.

[143]  P. Palese,et al.  7a Protein of Severe Acute Respiratory Syndrome Coronavirus Inhibits Cellular Protein Synthesis and Activates p38 Mitogen-Activated Protein Kinase , 2006, Journal of Virology.

[144]  J. Peiris,et al.  Severe acute respiratory syndrome coronavirus Orf3a protein interacts with caveolin. , 2007, The Journal of general virology.

[145]  Wanjin Hong,et al.  Over-expression of severe acute respiratory syndrome coronavirus 3b protein induces both apoptosis and necrosis in Vero E6 cells , 2006, Virus Research.

[146]  I. Braakman,et al.  Folding of Viral Envelope Glycoproteins in the Endoplasmic Reticulum , 2000, Traffic.

[147]  J. Maller.  MAP kinase activation , 1991, Current Biology.

[148]  C. Hsiao,et al.  Identification of a novel protein 3a from severe acute respiratory syndrome coronavirus , 2004, FEBS Letters.

[149]  V. Chow,et al.  The nonstructural protein 8 (nsp8) of the SARS coronavirus interacts with its ORF6 accessory protein , 2007, Virology.

[150]  W. Hong,et al.  The human severe acute respiratory syndrome coronavirus (SARS-CoV) 8b protein is distinct from its counterpart in animal SARS-CoV and down-regulates the expression of the envelope protein in infected cells , 2006, Virology.

[151]  Z. Yao,et al.  Nucleolar localization of non-structural protein 3b, a protein specifically encoded by the severe acute respiratory syndrome coronavirus , 2005, Virus Research.

[152]  Zihe Rao,et al.  Structural insights into SARS coronavirus proteins , 2005, Current Opinion in Structural Biology.

[153]  S. Lal,et al.  SARS-CoV accessory protein 3b induces AP-1 transcriptional activity through activation of JNK and ERK pathways. , 2011, Biochemistry.

[154]  D. Fremont,et al.  Structure, Expression, and Intracellular Localization of the SARS-CoV Accessory Proteins 7a and 7b , 2006, Advances in experimental medicine and biology.

[155]  P. Rottier,et al.  The Group-Specific Murine Coronavirus Genes Are Not Essential, but Their Deletion, by Reverse Genetics, Is Attenuating in the Natural Host , 2002, Virology.

[156]  F. Weber,et al.  Middle East Respiratory Syndrome Coronavirus Accessory Protein 4a Is a Type I Interferon Antagonist , 2013, Journal of Virology.

[157]  W. Hong,et al.  Genetic lesions within the 3a gene of SARS-CoV , 2005, Virology Journal.

[158]  A. Mirazimi,et al.  Inhibition of SARS-CoV replication cycle by small interference RNAs silencing specific SARS proteins, 7a/7b, 3a/3b and S , 2006, Antiviral Research.

[159]  H. Klenk,et al.  Isolated HE-protein from hemagglutinating encephalomyelitis virus and bovine coronavirus has receptor-destroying and receptor-binding activity , 1991, Virology.

[160]  K. Yuen,et al.  Differential maturation and subcellular localization of severe acute respiratory syndrome coronavirus surface proteins S, M and E. , 2005, The Journal of general virology.

[161]  Runsheng Chen,et al.  Antibody responses to individual proteins of SARS coronavirus and their neutralization activities , 2005, Microbes and Infection.