PubMed Journals: J Virol
Source: PMID: 17715225
⇦ ⇨ J Virol. 2007 Nov;81(21):11620-33. Epub
⇩ 2007 Aug 22.
Severe acute respiratory syndrome coronavirus
evades antiviral signaling: role of nsp1
and rational design of an attenuated strain.
Wathelet MG(1), Orr M, Frieman MB, Baric
(1) Department of Molecular and Cellular
Physiology, University of Cincinnati College
of Medicine, 231 Albert Sabin Way, Cincinnati,
OH 45267-0576, USA. email@example.com
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 nonstructural
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, mutant virus replication was strongly
attenuated in cells with an intact IFN response.
Thus, nsp1 is likely a virulence factor
that contributes to pathogenicity by favoring
DOI: 10.1128/JVI.00702-07 PMCID: PMC2168762
PMID: 17715225 [Indexed for MEDLINE]