Severe acute respiratory syndrome coronavirus protein 6 accelerates murine coronavirus infections

Chandra Tangudu; Heidi Olivares; Jason Netland; Stanley Perlman; Thomas Gallagher

doi:10.1128/JVI.01515-06

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Severe acute respiratory syndrome coronavirus protein 6 accelerates murine coronavirus infections

Journal article

Open access

Peer reviewed

Severe acute respiratory syndrome coronavirus protein 6 accelerates murine coronavirus infections

Chandra Tangudu, Heidi Olivares, Jason Netland, Stanley Perlman and Thomas Gallagher

Journal of virology, Vol.81(3), pp.1220-1229

02/2007

DOI: 10.1128/JVI.01515-06

PMCID: PMC1797517

PMID: 17108045

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Abstract

One or more of the unique 3'-proximal open reading frames (ORFs) of the severe acute respiratory syndrome (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 (L. Pewe, H. Zhou, J. Netland, C. Tangudu, H. Olivares, L. Shi, D. Look, T. Gallagher, and S. Perlman, J. Virol. 79:11335-11342, 2005). 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 infections did. 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 the virus entry or assembly stage, as virions from either infection were indistinguishable. Rather, protein 6 appeared to operate by fostering viral RNA and protein synthesis, as RNA quantifications by reverse transcription-quantitative PCR revealed viral RNA levels in the rJ.6 cultures that were five to eight times higher than those lacking protein 6. Furthermore, protein 6 coimmunoprecipitated with viral RNAs and colocalized 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.

Animals

Coronavirus Infections - veterinary

Coronavirus Infections - virology

Virulence - genetics

Humans

Viral Nonstructural Proteins - genetics

Mice

HeLa Cells

Open Reading Frames - genetics

SARS Virus - chemistry

Virus Replication - physiology

Viral Nonstructural Proteins - physiology

Details

Title: Subtitle: Severe acute respiratory syndrome coronavirus protein 6 accelerates murine coronavirus infections
Creators: Chandra Tangudu - Department of Microbiology and Immunology, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA
Heidi Olivares
Jason Netland
Stanley Perlman
Thomas Gallagher
Resource Type: Journal article
Publication Details: Journal of virology, Vol.81(3), pp.1220-1229
DOI: 10.1128/JVI.01515-06
PMID: 17108045
PMCID: PMC1797517
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: United States
Grant note: P01 AI060699 / NIAID NIH HHS
Language: English
Date published: 02/2007
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777346202771

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