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S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients.
J Virol. 2004 Jun; 78(12):6134-42.JV

Abstract

The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes severe pneumonia with a fatal outcome in approximately 10% of patients. SARS-CoV is not closely related to other coronaviruses but shares a similar genome organization. Entry of coronaviruses into target cells is mediated by the viral S protein. We functionally analyzed SARS-CoV S using pseudotyped lentiviral particles (pseudotypes). The SARS-CoV S protein was found to be expressed at the cell surface upon transient transfection. Coexpression of SARS-CoV S with human immunodeficiency virus-based reporter constructs yielded viruses that were infectious for a range of cell lines. Most notably, viral pseudotypes harboring SARS-CoV S infected hepatoma cell lines but not T- and B-cell lines. Infection of the hepatoma cell line Huh-7 was also observed with replication-competent SARS-CoV, indicating that hepatocytes might be targeted by SARS-CoV in vivo. Inhibition of vacuolar acidification impaired infection by SARS-CoV S-bearing pseudotypes, indicating that S-mediated entry requires low pH. Finally, infection by SARS-CoV S pseudotypes but not by vesicular stomatitis virus G pseudotypes was efficiently inhibited by a rabbit serum raised against SARS-CoV particles and by sera from SARS patients, demonstrating that SARS-CoV S is a target for neutralizing antibodies and that such antibodies are generated in SARS-CoV-infected patients. Our results show that viral pseudotyping can be employed for the analysis of SARS-CoV S function. Moreover, we provide evidence that SARS-CoV infection might not be limited to lung tissue and can be inhibited by the humoral immune response in infected patients.

Authors+Show Affiliations

Institute for Clinical and Molecular Virology, University Erlangen-Nürnberg, Nikolaus-Fiebiger-Center, Glückstrasse 6, D-91054 Erlangen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15163706

Citation

Hofmann, Heike, 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." Journal of Virology, vol. 78, no. 12, 2004, pp. 6134-42.
Hofmann H, Hattermann K, Marzi A, 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. J Virol. 2004;78(12):6134-42.
Hofmann, H., Hattermann, K., Marzi, A., Gramberg, T., Geier, M., Krumbiegel, M., Kuate, S., Uberla, K., Niedrig, M., & Pöhlmann, S. (2004). S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients. Journal of Virology, 78(12), 6134-42.
Hofmann H, 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. J Virol. 2004;78(12):6134-42. PubMed PMID: 15163706.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients. AU - Hofmann,Heike, AU - Hattermann,Kim, AU - Marzi,Andrea, AU - Gramberg,Thomas, AU - Geier,Martina, AU - Krumbiegel,Mandy, AU - Kuate,Seraphin, AU - Uberla,Klaus, AU - Niedrig,Matthias, AU - Pöhlmann,Stefan, PY - 2004/5/28/pubmed PY - 2004/6/30/medline PY - 2004/5/28/entrez SP - 6134 EP - 42 JF - Journal of virology JO - J Virol VL - 78 IS - 12 N2 - The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes severe pneumonia with a fatal outcome in approximately 10% of patients. SARS-CoV is not closely related to other coronaviruses but shares a similar genome organization. Entry of coronaviruses into target cells is mediated by the viral S protein. We functionally analyzed SARS-CoV S using pseudotyped lentiviral particles (pseudotypes). The SARS-CoV S protein was found to be expressed at the cell surface upon transient transfection. Coexpression of SARS-CoV S with human immunodeficiency virus-based reporter constructs yielded viruses that were infectious for a range of cell lines. Most notably, viral pseudotypes harboring SARS-CoV S infected hepatoma cell lines but not T- and B-cell lines. Infection of the hepatoma cell line Huh-7 was also observed with replication-competent SARS-CoV, indicating that hepatocytes might be targeted by SARS-CoV in vivo. Inhibition of vacuolar acidification impaired infection by SARS-CoV S-bearing pseudotypes, indicating that S-mediated entry requires low pH. Finally, infection by SARS-CoV S pseudotypes but not by vesicular stomatitis virus G pseudotypes was efficiently inhibited by a rabbit serum raised against SARS-CoV particles and by sera from SARS patients, demonstrating that SARS-CoV S is a target for neutralizing antibodies and that such antibodies are generated in SARS-CoV-infected patients. Our results show that viral pseudotyping can be employed for the analysis of SARS-CoV S function. Moreover, we provide evidence that SARS-CoV infection might not be limited to lung tissue and can be inhibited by the humoral immune response in infected patients. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/15163706/S_protein_of_severe_acute_respiratory_syndrome_associated_coronavirus_mediates_entry_into_hepatoma_cell_lines_and_is_targeted_by_neutralizing_antibodies_in_infected_patients_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=15163706 DB - PRIME DP - Unbound Medicine ER -