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			PubMed Journals: J Virol

  Source:		PMID: 17715225
  Download:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2168762/pdf/0702-07.pdf

    		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
			RS.

			Author Information
			(1) Department of Molecular and Cellular
			Physiology, University of Cincinnati College
			of Medicine, 231 Albert Sabin Way, Cincinnati,
			OH 45267-0576, USA. marc.wathelet@uc.edu

			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
			SARS-CoV replication.

			DOI: 10.1128/JVI.00702-07 PMCID: PMC2168762
			PMID: 17715225 [Indexed for MEDLINE]

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