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. 2004 Apr 23;279(17):17158-64.
doi: 10.1074/jbc.M312144200. Epub 2004 Feb 11.

V体育官网 - Hepatitis C virus suppresses the IRE1-XBP1 pathway of the unfolded protein response

Keith D Tardif  1 , Kazutoshi Mori, Randal J Kaufman, Aleem Siddiqui
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Hepatitis C virus suppresses the IRE1-XBP1 pathway of the unfolded protein response (V体育平台登录)

Keith D Tardif et al. J Biol Chem. .
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Abstract

Hepatitis C virus (HCV) gene expression disrupts normal endoplasmic reticulum (ER) functions and induces ER stress. ER stress results from the accumulation of unfolded or misfolded proteins in the ER; cells can alleviate this stress by degrading or refolding these proteins. The IRE1-XBP1 pathway directs both protein refolding and degradation in response to ER stress. Like IRE1-XBP1, other branches of the ER stress response mediate protein refolding. However, IRE1-XBP1 can also specifically activate protein degradation. We show here that XBP1 expression is elevated in cells carrying HCV subgenomic replicons, but XBP1 trans-activating activity is repressed. This prevents the IRE1-XBP1 transcriptional induction of EDEM (ER degradation-enhancing alpha-mannosidase-like protein) VSports手机版. The mRNA expression of EDEM is required for the degradation of misfolded proteins. Consequently, misfolded proteins are stable in cells expressing HCV replicons. HCV may suppress the IRE1-XBP1 pathway to stimulate the synthesis of its viral proteins. IRE1alpha-null MEFs, a cell line with a defective IRE1-XBP1 pathway, show elevated levels of HCV IRES-mediated translation. Therefore, HCV may suppress the IRE1-XBP1 pathway to not only promote HCV expression but also to contribute to the persistence of the virus in infected hepatocytes. .

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