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A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration

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  1. Structure-Guided Identification of a Family of Dual Receptor-Binding PfEMP1 that Is Associated with Cerebral Malaria

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  2. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes

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  1. Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis

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  2. Evolutionary selection of pestivirus variants with altered or no microRNA dependency

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  3. Replicons of a rodent hepatitis C model virus permit selection of highly permissive cells

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  4. Functional Interplay between RNA Viruses and Non-Coding RNA in Mammals

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  5. Viral persistence, liver disease and host response in Hepatitis C-like virus rat model

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  • Troels K H Scheel
  • Joseph M Luna
  • Matthias Liniger
  • Eiko Nishiuchi
  • Kathryn Rozen-Gagnon
  • Amir Shlomai
  • Gaël Auray
  • Markus Gerber
  • John Fak
  • Irene Keller
  • Rémy Bruggmann
  • Robert B Darnell
  • Nicolas Ruggli
  • Charles M Rice
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Small non-coding RNAs have emerged as key modulators of viral infection. However, with the exception of hepatitis C virus, which requires the liver-specific microRNA (miRNA)-122, the interactions of RNA viruses with host miRNAs remain poorly characterized. Here, we used crosslinking immunoprecipitation (CLIP) of the Argonaute (AGO) proteins to characterize strengths and specificities of miRNA interactions in the context of 15 different RNA virus infections, including several clinically relevant pathogens. Notably, replication of pestiviruses, a major threat to milk and meat industries, critically depended on the interaction of cellular miR-17 and let-7 with the viral 3' UTR. Unlike canonical miRNA interactions, miR-17 and let-7 binding enhanced pestivirus translation and RNA stability. miR-17 sequestration by pestiviruses conferred reduced AGO binding and functional de-repression of cellular miR-17 targets, thereby altering the host transcriptome. These findings generalize the concept of RNA virus dependence on cellular miRNAs and connect virus-induced miRNA sequestration to host transcriptome regulation.

Original languageEnglish
JournalCell Host & Microbe
Volume19
Issue number3
Pages (from-to)409-23
Number of pages15
ISSN1931-3128
DOIs
Publication statusPublished - 9 Mar 2016

ID: 46380623