Carlton-Smith, C. and Elliott, R.M. (2012) Viperin, MTAP44, and protein kinase R contribute to the interferon-induced inhibition of Bunyamwera orthobunyavirus replication. Journal of Virology, 86(21), pp. 11548-11557. (doi: 10.1128/JVI.01773-12)
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Abstract
The first line of defence against viral infection is the interferon (IFN) response, which culminates in the expression of hundreds of proteins with presumed antiviral activity, and must be overcome by a virus for successful replication. The non-structural NSs protein is the primary IFN antagonist encoded by Bunyamwera virus (BUNV), the prototype of the <i>Orthobunyavirus</i> genus and the family <i>Bunyaviridae</i>. The NSs protein interferes with RNA polymerase II-mediated transcription thereby inhibiting cellular mRNA production, including IFN mRNAs. A recombinant virus, rBUNdelNSs, that is unable to express the NSs protein, does not inhibit cellular transcription and is a strong IFN inducer. We report here that cells stimulated into the antiviral state by IFNβ treatment were protected against wtBUNV and rBUNdelNSs infection but addition of IFNβ after infection had little effect on the replication cycle of either virus. By screening a panel of cell lines that over-expressed individual IFN stimulated genes, we found that PKR, MTAP44 and particularly viperin appreciably restricted BUNV replication. The enzymatic activities of PKR and viperin were required for their inhibitory activity. Taken together, our data show that the restriction of BUNV replication mediated by IFN is an accumulated effect of at least three ISGs that probably act on different stages of the viral replication cycle.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Elliott, Professor Richard |
| Authors: | Carlton-Smith, C., and Elliott, R.M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Journal of Virology |
| ISSN: | 0022-538X |
| ISSN (Online): | 1098-5514 |
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