Research ArticleImmunology

IRE1α promotes viral infection by conferring resistance to apoptosis

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Sci. Signal.  06 Jun 2017:
Vol. 10, Issue 482, eaai7814
DOI: 10.1126/scisignal.aai7814

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Resisting death by virus

The unfolded protein response (UPR) alleviates the cellular stress caused by the accumulation of proteins, such as that occurring during viral infection. During the UPR, processing of Xbp1 mRNA by the nuclease IRE1α generates the transcription factor XBP1, which drives the expression of genes encoding type I interferons (IFNs). Fink et al. found that Xbp1-deficient cells had defective antiviral responses to infection by hepatitis C virus (HCV); however, the cells were not compromised in type I IFN production or responses. Instead, these cells showed increased activation of IRE1α, which cleaved the proapoptotic microRNA miR-125a, leading to decreased apoptosis and increased viral replication. Liver biopsies from HCV-infected patients also showed increased IRE1α activation and decreased miR-125a abundance. Together, these data suggest that IRE1α functions to enhance cell survival in response to viral infection and may provide a potential therapeutic target.