Cellular entry of the SARS coronavirus

Enveloped viruses have evolved membrane glycoproteins (GPs) that mediate entry into host cells. These proteins are important targets for antiviral therapies and vaccines. Several efforts to understand and combat infection by severe acute respiratory syndrome coronavirus (SARS-CoV) have therefore focused on the viral GP, known as spike (S). In a short period of time, important aspects of SARS-CoV S-protein function were unraveled. The identification of angiotensin-converting enzyme 2 (ACE2) as a receptor for SARS-CoV provided an insight into viral tropism and pathogenesis, whereas mapping of functional domains in the S-protein enabled inhibitors to be generated. Vaccines designed on the basis of SARS-CoV S-protein were shown to be effective in animals and consequently are attractive candidates for vaccine trials in humans. Here, we discuss how SARS-CoV S facilitates viral entry into target cells and illustrate current approaches that are used to inhibit this process.

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

[2]  D. Dimitrov,et al.  A model of the ACE2 structure and function as a SARS-CoV receptor , 2003, Biochemical and Biophysical Research Communications.

[3]  D. Dimitrov The Secret Life of ACE2 as a Receptor for the SARS Virus , 2003, Cell.

[4]  W. Thomas,et al.  Amino Acids 270 to 510 of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Are Required for Interaction with Receptor , 2004, Journal of Virology.

[5]  K. Subbarao,et al.  pH-Dependent Entry of Severe Acute Respiratory Syndrome Coronavirus Is Mediated by the Spike Glycoprotein and Enhanced by Dendritic Cell Transfer through DC-SIGN , 2004, Journal of Virology.

[6]  R. Levis,et al.  Multiple receptor-dependent steps determine the species specificity of HCV-229E infection. , 1995, Advances in experimental medicine and biology.

[7]  Nigel M. Hooper,et al.  A Human Homolog of Angiotensin-converting Enzyme , 2000, The Journal of Biological Chemistry.

[8]  J. Kilby,et al.  Novel therapies based on mechanisms of HIV-1 cell entry. , 2003, The New England journal of medicine.

[9]  J. Lepault,et al.  Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Sung,et al.  Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection , 2003, Gastroenterology.

[11]  Ari Helenius,et al.  How Viruses Enter Animal Cells , 2004, Science.

[12]  Saurabh Menon,et al.  ACE2 X-Ray Structures Reveal a Large Hinge-bending Motion Important for Inhibitor Binding and Catalysis , 2004, Journal of Biological Chemistry.

[13]  M. Enserink One Year After Outbreak, SARS Virus Yields Some Secrets , 2004, Science.

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

[15]  D. Dimitrov,et al.  Virus entry: molecular mechanisms and biomedical applications , 2004, Nature Reviews Microbiology.

[16]  Malik Peiris,et al.  Aetiology: Koch's postulates fulfilled for SARS virus , 2003, Nature.

[17]  Gary J. Nabel,et al.  A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice , 2004, Nature.

[18]  Arul Earnest,et al.  Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. , 2003, JAMA.

[19]  Michelle M. Packard,et al.  Prior Infection and Passive Transfer of Neutralizing Antibody Prevent Replication of Severe Acute Respiratory Syndrome Coronavirus in the Respiratory Tract of Mice , 2004, Journal of Virology.

[20]  J. Peiris,et al.  Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome , 2003, The Lancet.

[21]  R. Hodges,et al.  Structural Characterization of the SARS-Coronavirus Spike S Fusion Protein Core , 2004, Journal of Biological Chemistry.

[22]  G. Gao,et al.  Following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors , 2004, Biochemical and Biophysical Research Communications.

[23]  Xiaolei Yin,et al.  Expression cloning of functional receptor used by SARS coronavirus , 2004, Biochemical and Biophysical Research Communications.

[24]  M. Crackower,et al.  Angiotensin-converting enzyme 2 is an essential regulator of heart function , 2002, Nature.

[25]  M. Buchmeier,et al.  Coronavirus Spike Proteins in Viral Entry and Pathogenesis , 2001, Virology.

[26]  P. Talbot,et al.  Coronavirus Hcov-229e of the Spike Glycoprotein of Human Identification of a Receptor-binding Domain , 2002 .

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

[28]  Xin Li,et al.  The clinical pathology of severe acute respiratory syndrome (SARS): a report from China , 2003, The Journal of pathology.

[29]  J. A. Comer,et al.  A novel coronavirus associated with severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[30]  W. Bellini,et al.  Effects of a SARS-associated coronavirus vaccine in monkeys , 2003, The Lancet.

[31]  A. Steinkasserer,et al.  DC-SIGN and DC-SIGNR Interact with the Glycoprotein of Marburg Virus and the S Protein of Severe Acute Respiratory Syndrome Coronavirus , 2004, Journal of Virology.

[32]  B. Murphy,et al.  An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus , 2004, Nature Medicine.

[33]  B. Bosch,et al.  The Coronavirus Spike Protein Is a Class I Virus Fusion Protein: Structural and Functional Characterization of the Fusion Core Complex , 2003, Journal of Virology.

[34]  Y. Guan,et al.  Coronavirus as a possible cause of severe acute respiratory syndrome , 2003, The Lancet.

[35]  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.

[36]  B. Delmas,et al.  Determinants essential for the transmissible gastroenteritis virus-receptor interaction reside within a domain of aminopeptidase-N that is distinct from the enzymatic site , 1994, Journal of virology.

[37]  P S Kim,et al.  Mechanisms of viral membrane fusion and its inhibition. , 2001, Annual review of biochemistry.

[38]  D. Dimitrov,et al.  The SARS-CoV S glycoprotein: expression and functional characterization , 2003, Biochemical and Biophysical Research Communications.

[39]  Qingling Zhang,et al.  Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS‐CoV) in SARS patients: implications for pathogenesis and virus transmission pathways , 2004, The Journal of pathology.

[40]  G. Simmons,et al.  Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Yi Guan,et al.  Lung pathology of fatal severe acute respiratory syndrome , 2003, The Lancet.

[42]  A. J. Gibbs,et al.  The phylogeny of SARS coronavirus , 2004, Archives of Virology.

[43]  Wenhui Li,et al.  A 193-Amino Acid Fragment of the SARS Coronavirus S Protein Efficiently Binds Angiotensin-converting Enzyme 2* , 2004, Journal of Biological Chemistry.

[44]  B. Bosch,et al.  Cleavage Inhibition of the Murine Coronavirus Spike Protein by a Furin-Like Enzyme Affects Cell-Cell but Not Virus-Cell Fusion , 2004, Journal of Virology.

[45]  G. Fey,et al.  Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor , 2004, Biochemical and Biophysical Research Communications.

[46]  F. Taguchi The S2 subunit of the murine coronavirus spike protein is not involved in receptor binding , 1995, Journal of virology.

[47]  L. Poon,et al.  Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia : a prospective study , 2003 .

[48]  G. Navis,et al.  Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis , 2004, The Journal of pathology.

[49]  Christian Drosten,et al.  Identification of a novel coronavirus in patients with severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[50]  A. Debnath,et al.  Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors , 2004, The Lancet.

[51]  M. Raamsman,et al.  Retargeting of Coronavirus by Substitution of the Spike Glycoprotein Ectodomain: Crossing the Host Cell Species Barrier , 2000, Journal of Virology.

[52]  B. Moss,et al.  Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[53]  G. Tse,et al.  Tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in‐situ hybridization study of fatal cases , 2004, The Journal of pathology.

[54]  K. Überla,et al.  S Protein of Severe Acute Respiratory Syndrome-Associated Coronavirus Mediates Entry into Hepatoma Cell Lines and Is Targeted by Neutralizing Antibodies in Infected Patients , 2004, Journal of Virology.

[55]  Y. Kooyk,et al.  DC-SIGN: escape mechanism for pathogens , 2003, Nature Reviews Immunology.

[56]  Wenhui Li,et al.  Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[57]  R. Rappuoli,et al.  SARS — beginning to understand a new virus , 2003, Nature Reviews Microbiology.

[58]  S. Perlman,et al.  Pathogenesis of coronavirus-induced infections. Review of pathological and immunological aspects. , 1998, Advances in experimental medicine and biology.

[59]  A. Carfi,et al.  Structural characterization of the fusion-active complex of severe acute respiratory syndrome (SARS) coronavirus. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[60]  B. Berkhout,et al.  Identification of a new human coronavirus , 2004, Nature Medicine.

[61]  John L. Sullivan,et al.  Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus , 2003, Nature.