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
Virologyjournal_title
Virologyauthors
Cruz CC,Suthar MS,Montgomery SA,Shabman R,Simmons J,Johnston RE,Morrison TE,Heise MTdoi
10.1016/j.virol.2009.12.031subject
Has Abstractpub_date
2010-03-30 00:00:00pages
1-10issue
1eissn
0042-6822issn
1096-0341pii
S0042-6822(09)00816-2journal_volume
399pub_type
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