This Article Full Text (PDF) Other Versions of this Article: JVI.00702-07v1 81/21/11620    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wathelet, M. G. Articles by Baric, R. S. Search for Related Content PubMed PubMed Citation Articles by Wathelet, M. G. Articles by Baric, R. S.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.00702-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The SARS coronavirus evades antiviral signaling: role of nsp1 and rational design of an attenuated strain

Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH45267-0576, U.S.A.; Departments of Epidemiology and Microbiology and Immunology and; Carolina Vaccine Institute, University of North Carolina, Chapel Hill, NC 27599-7435, U.S.A.

^* To whom correspondence should be addressed. Email: marc.wathelet{at}uc.edu.

	Abstract

The severe acute respiratory syndrome (SARS) epidemic was caused by the spread of a previously unrecognized infectious agent, the SARS-associated coronavirus (SARS-CoV). Here we show that SARS-CoV could inhibit both virus- and interferon (IFN)-dependent signaling, two key steps of the antiviral response. We mapped a strong inhibitory activity to SARS-CoV non-structural protein 1 (nsp1) and show that expression of nsp1 significantly inhibited the activation of all three virus-dependent signaling pathways. We show that expression of nsp1 significantly inhibited IFN-dependent signaling by decreasing the phosphorylation levels of STAT1, while having little effect on those of STAT2, JAK1 and TYK2. We engineered an attenuated mutant of nsp1 in SARS-CoV through reverse genetics and the resulting mutant virus was viable and replicated as efficiently as wild type virus in cells with a defective IFN response. However, the mutant virus replication was strongly attenuated in cells with an intact IFN response. Thus, nsp1 is likely a virulence factor that would contribute to pathogenicity by favoring SARS-CoV replication.

This article has been cited by other articles:

• Narayanan, K., Huang, C., Lokugamage, K., Kamitani, W., Ikegami, T., Tseng, C.-T. K., Makino, S. (2008). Severe Acute Respiratory Syndrome Coronavirus nsp1 Suppresses Host Gene Expression, Including That of Type I Interferon, in Infected Cells. J. Virol. 82: 4471-4479 [Abstract] [Full Text]  
• Bechill, J., Chen, Z., Brewer, J. W., Baker, S. C. (2008). Coronavirus Infection Modulates the Unfolded Protein Response and Mediates Sustained Translational Repression. J. Virol. 82: 4492-4501 [Abstract] [Full Text]