Modulation of type I IFN induction by a virulence determinant within the alphavirus nsP1 protein.
Modulation of type I IFN induction by a virulence determinant within the alphavirus nsP1 protein.
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DOI：
10.1016/j.virol.2009.12.031
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发表时间：
2010-03-30
期刊：
影响因子：
3.7
通讯作者：
Heise MT
中科院分区：
文献类型：
--
作者：
Cruz CC;Suthar MS;Montgomery SA;Shabman R;Simmons J;Johnston RE;Morrison TE;Heise MT
Alphaviruses are mosquito-borne viruses that cause serious human and animal diseases. Previous studies demonstrated that a determinant within the nsP1/nsP2 cleavage domain of the virulent Sindbis AR86 virus played a key role in regulating adult mouse virulence without adversely affecting viral replication. Additional characterization of this determinant demonstrated that a virus with the attenuating mutation induced more type I IFN production both in vivo and in vitro. Interestingly, this phenotype was not specific to the Sindbis AR86 virus, as a similar mutation in a distantly related alphavirus, Ross River Virus (RRV), also led to enhanced IFN induction. This effect was independent of virus-induced host shutoff, since IRF-3 phosphorylation, which occurs independently of de novo host transcription/translation, was induced more robustly in cells infected with the mutant viruses. Altogether, these results demonstrate that critical determinants within the nsP1/nsP2 cleavage domain play an important role in regulating alphavirus induced IFN responses.
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