Modulation of type I IFN induction by a virulence determinant within the alphavirus nsP1 protein.

Abstract:

: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.

journal_name

Virology

journal_title

Virology

authors

Cruz CC,Suthar MS,Montgomery SA,Shabman R,Simmons J,Johnston RE,Morrison TE,Heise MT

doi

10.1016/j.virol.2009.12.031

subject

Has Abstract

pub_date

2010-03-30 00:00:00

pages

1-10

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(09)00816-2

journal_volume

399

pub_type

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