title: A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration.
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.
authors.affiliation: 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.
authors.forename: Troels K H
authors.initials: TK
authors.lastname: Scheel
authors.affiliation: 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.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Luna
authors.affiliation: Department of Virology, Institute of Virology and Immunology IVI, 3147 Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, University of Bern, 3012 Bern, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Liniger
authors.affiliation: Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Eiko
authors.initials: E
authors.lastname: Nishiuchi
authors.affiliation: Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Rozen-Gagnon
authors.affiliation: Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Shlomai
authors.affiliation: Department of Virology, Institute of Virology and Immunology IVI, 3147 Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, University of Bern, 3012 Bern, Switzerland.
authors.forename: Gaël
authors.initials: G
authors.lastname: Auray
authors.affiliation: Department of Virology, Institute of Virology and Immunology IVI, 3147 Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, University of Bern, 3012 Bern, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Gerber
authors.affiliation: Laboratory of Molecular Neuro-Oncology, and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
authors.forename: John
authors.initials: J
authors.lastname: Fak
authors.affiliation: Interfaculty Bioinformatics Unit and Swiss Institute of Bioinformatics, University of Bern, 3012 Bern, Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Keller
authors.affiliation: Interfaculty Bioinformatics Unit and Swiss Institute of Bioinformatics, University of Bern, 3012 Bern, Switzerland.
authors.forename: Rémy
authors.initials: R
authors.lastname: Bruggmann
authors.affiliation: 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.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Darnell
authors.affiliation: Department of Virology, Institute of Virology and Immunology IVI, 3147 Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, University of Bern, 3012 Bern, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ruggli
authors.affiliation: 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.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
mesh_terms: D000818:Animals; D002460:Cell Line; D054884:Host-Pathogen Interactions; D047468:Immunoprecipitation; D035683:MicroRNAs / Q000378:metabolism*; D014176:Protein Biosynthesis; D020871:RNA Stability; D012328:RNA Viruses / Q000502:physiology*; D012367:RNA, Viral / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral
keywords: Argonaute; CLIP-Seq; HiTS-CLIP; bovine viral diarrhea virus; hepatitis C virus; miRNA; pestivirus; sponge