Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors

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Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors

Hepatitis C virus (HCV) replication is dependent on a liver-specific microRNA (miRNA), miR-122. A recent clinical trial reported that transient inhibition of miR-122 reduced viral titres in HCV-infected patients. Here we set out to better understand how miR-122 inhibition influences HCV replication over time. Unexpectedly, we observed the emergence of an HCV variant that is resistant to miR-122...

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Hepatitis C Virus RNA Functionally Sequesters miR-122

Hepatitis C virus (HCV) uniquely requires the liver-specific microRNA-122 for replication, yet global effects on endogenous miRNA targets during infection are unexplored. Here, high-throughput sequencing and crosslinking immunoprecipitation (HITS-CLIP) experiments of human Argonaute (AGO) during HCV infection showed robust AGO binding on the HCV 5'UTR at known and predicted miR-122 sites. On th...

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Viral Determinants of miR-122-Independent Hepatitis C Virus Replication

Hepatitis C virus (HCV) replication requires binding of the liver-specific microRNA (miRNA) miR-122 to two sites in the HCV 5' untranslated region (UTR). Although we and others have shown that viral genetics impact the amount of active miR-122 required for replication, it is unclear if HCV can replicate in the complete absence of this miRNA. To probe the absolute requirements for miR-122 and th...

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miR-122-induced down-regulation of HO-1 negatively affects miR-122-mediated suppression of HBV.

As the most abundant liver-specific microRNA (miRNA), miR-122 has been extensively studied for its role in the regulation of lipid metabolism, hepatocarcinogenesis and hepatitis C virus (HCV) replication, but little is known regarding its role in the replication of Hepatitis B virus (HBV), a highly prevalent hepatotropic virus that can cause life-threatening complications. In this study we exam...

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S ince the discovery in 2005 of the essential role of the liver-specific microRNA, miR-122, in HCV replication (1), the mechanism by which it stimulates this process has proved elusive. In PNAS, Li et al. demonstrate thatmiR-122 acts to shield the HCV genome against degradation by the cytosolic RNA exonuclease, Xrn1 (2). Although this may be one way in which this microRNA promotes HCV replicati...

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ژورنال

عنوان ژورنال: Nature Communications

سال: 2014

ISSN: 2041-1723

DOI: 10.1038/ncomms6408