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

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

doi:10.1016/j.chom.2016.02.007

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

Cell Host Microbe. 2016 Mar 9;19(3):409-23. doi: 10.1016/j.chom.2016.02.007.

Authors

Affiliations

¹ Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA; Copenhagen Hepatitis C Program, Department of Infectious Diseases and Clinical Research Centre, Copenhagen University Hospital, 2650 Hvidovre, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
² Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA; Laboratory of Molecular Neuro-Oncology, and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
³ Department of Virology, Institute of Virology and Immunology IVI, 3147 Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, University of Bern, 3012 Bern, Switzerland.
⁴ Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
⁵ Laboratory of Molecular Neuro-Oncology, and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
⁶ Interfaculty Bioinformatics Unit and Swiss Institute of Bioinformatics, University of Bern, 3012 Bern, Switzerland.
⁷ Laboratory of Molecular Neuro-Oncology, and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA; New York Genome Center, New York, NY 10013, USA.
⁸ Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA. Electronic address: ricec@rockefeller.edu.

Abstract

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.

Keywords: Argonaute; CLIP-Seq; HiTS-CLIP; bovine viral diarrhea virus; hepatitis C virus; miRNA; pestivirus; sponge.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Host-Pathogen Interactions*
Immunoprecipitation
MicroRNAs / metabolism*
Protein Biosynthesis
RNA Stability
RNA Viruses / physiology*
RNA, Viral / metabolism*
Virus Replication

Substances

MicroRNAs
RNA, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding