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. © 2009 Elsevier Inc. All rights reserved.
Cruz, C. C., Suthar, M. S., Montgomery, S. A., Shabman, R., Simmons, J., Johnston, R. E., … Heise, M. T. (2010). Modulation of type I IFN induction by a virulence determinant within the alphavirus nsP1 protein. Virology, 399(1), 1–10. https://doi.org/10.1016/j.virol.2009.12.031