| First Author | Stirnweiss A | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 9 | Pages | 5179-85 |
| PubMed ID | 20308629 | Mgi Jnum | J:160488 |
| Mgi Id | MGI:4454517 | Doi | 10.4049/jimmunol.0902264 |
| Citation | Stirnweiss A, et al. (2010) IFN regulatory factor-1 bypasses IFN-mediated antiviral effects through viperin gene induction. J Immunol 184(9):5179-85 |
| abstractText | Viperin is an antiviral protein whose expression is highly upregulated during viral infections via IFN-dependent and/or IFN-independent pathways. We examined the molecular alterations induced by the transcriptional activator IFN regulatory factor (IRF)-1 and found viperin to be among the group of IRF-1 regulated genes. From these data, it was not possible to distinguish genes that are primary targets of IRF-1 and those that are targets of IRF-1-induced proteins, like IFN-beta. In this study, we show that IRF-1 directly binds to the murine viperin promoter to the two proximal IRF elements and thereby induces viperin expression. Infection studies with embryonal fibroblasts from different gene knock-out mice demonstrate that IRF-1 is essential, whereas the type I IFN system is dispensable for vesicular stomatitis virus induced viperin gene transcription. Further, IRF-1, but not IFN type I, mediates the induction of viperin transcription after IFN-gamma treatment. In contrast, IRF-1 is not required for IFN-independent viperin induction by Newcastle disease virus infection and by infection with a vesicular stomatitis virus mutant that is unable to block IFN expression and secretion. We conclude that the IRF-1 mediated type I IFN independent mechanism of enhanced viperin expression provides a redundant mechanism to protect cells from viral infections. This mechanism becomes important when viruses evade innate immunity by antagonizing the induction and function of the IFN system. |
