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Severe acute respiratory syndrome coronavirus evades antiviral signaling : Role of nspl and rational design of an attenuated strain

Identifieur interne : 003C87 ( Main/Merge ); précédent : 003C86; suivant : 003C88

Severe acute respiratory syndrome coronavirus evades antiviral signaling : Role of nspl and rational design of an attenuated strain

Auteurs : Marc G. Wathelet [États-Unis] ; Melissa Orr [États-Unis] ; Matthew B. Frieman [États-Unis] ; Ralph S. Baric [États-Unis]

Source :

RBID : Pascal:07-0500880

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English descriptors

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 nonstructural protein 1 (nspl) and show that expression of nspl significantly inhibited the activation of all three virus-dependent signaling pathways. We show that expression of nspl 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 nspl 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, nspl is likely a virulence factor that contributes to pathogenicity by favoring SARS-CoV replication.

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Pascal:07-0500880

Le document en format XML

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