This Article Full Text (PDF) Other Versions of this Article: JVI.01515-06v1 81/3/1220    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 Tangudu, C. Articles by Gallagher, T. Search for Related Content PubMed PubMed Citation Articles by Tangudu, C. Articles by Gallagher, T.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.01515-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

SARS Coronavirus Protein 6 Accelerates Murine Coronavirus Infections

Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL; Interdisciplinary Program in Immunology and Department of Microbiology, University of Iowa, Iowa City, IA

^* To whom correspondence should be addressed. Email: tgallag{at}lumc.edu.

	Abstract

One or more of the unique 3'-proximal open reading frames (ORFs) of the SARS coronavirus may encode determinants of virus virulence. A prime candidate is ORF6, which encodes a 63-amino acid membrane-associated peptide that can dramatically increase the lethality of an otherwise attenuated JHM strain of murine coronavirus (Pewe et al., 2005, J. Virol., 79:11335). To discern virulence mechanisms, we compared the in vitro growth properties of rJ.6, a recombinant JHM expressing the SARS peptide, with isogenic rJ.6-KO, which has an inactive ORF containing a mutated initiation codon and a termination codon at internal position 27. The rJ.6 infections proceeded rapidly, secreting progeny about 1.5 h earlier than rJ.6-KO. The rJ.6 infections were also set apart by early viral protein accumulation and by robust expansion via syncytia, a characteristic feature of JHM virus dissemination. We found no evidence for protein 6 operating at virus entry or assembly stages, as virions from either infection were indistinguishable. Rather, protein 6 appeared to operate by fostering viral RNA and protein synthesis, as RNA quantifications by RT-qPCR revealed viral RNA levels in the rJ.6 cultures that were 5 to 8 times higher than those lacking protein 6. Furthermore, protein 6 co-immunoprecipitated with viral RNAs and co-localized on cytoplasmic vesicles with replicating viral RNAs. The SARS coronavirus encodes a novel membrane protein 6 that can accelerate replication of a related mouse virus, a property that may explain its ability to increase in vivo virus virulence.

This article has been cited by other articles:

• Hussain, S., Perlman, S., Gallagher, T. M. (2008). Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Hepatitis Virus Infections by More than One Mechanism. J. Virol. 82: 7212-7222 [Abstract] [Full Text]  
• Netland, J., Ferraro, D., Pewe, L., Olivares, H., Gallagher, T., Perlman, S. (2007). 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. J. Virol. 81: 11520-11525 [Abstract] [Full Text]  
• Cheng, V. C. C., Lau, S. K. P., Woo, P. C. Y., Yuen, K. Y. (2007). Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging Infection. Clin. Microbiol. Rev. 20: 660-694 [Abstract] [Full Text]  
• Frieman, M., Yount, B., Heise, M., Kopecky-Bromberg, S. A., Palese, P., Baric, R. S. (2007). Severe Acute Respiratory Syndrome Coronavirus ORF6 Antagonizes STAT1 Function by Sequestering Nuclear Import Factors on the Rough Endoplasmic Reticulum/Golgi Membrane. J. Virol. 81: 9812-9824 [Abstract] [Full Text]  
• Huang, C., Peters, C. J., Makino, S. (2007). Severe Acute Respiratory Syndrome Coronavirus Accessory Protein 6 Is a Virion-Associated Protein and Is Released from 6 Protein-Expressing Cells. J. Virol. 81: 5423-5426 [Abstract] [Full Text]