title: ATP-dependent effector-like functions of RIG-I-like receptors.
abstract: The vertebrate antiviral innate immune system is often considered to consist of two distinct groups of proteins: pattern recognition receptors (PRRs) that detect viral infection and induce the interferon (IFN) signaling, and effectors that directly act against viral replication. Accordingly, previous studies on PRRs, such as RIG-I and MDA5, have primarily focused on their functions in viral double-stranded RNA (dsRNA) detection and consequent antiviral signaling. We report here that both RIG-I and MDA5 efficiently displace viral proteins pre-bound to dsRNA in a manner dependent on their ATP hydrolysis, and that this activity assists a dsRNA-dependent antiviral effector protein, PKR, and allows RIG-I to promote MDA5 signaling. Furthermore, truncated RIG-I/MDA5 lacking the signaling domain, and hence the IFN stimulatory activity, displaces viral proteins and suppresses replication of certain viruses in an ATP-dependent manner. Thus, this study reveals novel "effector-like" functions of RIG-I and MDA5 that challenge the conventional view of PRRs.
authors.affiliation: Program in Cellular and Molecular Medicine, Children's Hospital Boston, MA 02115, USA.|State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences Nankai University, Tianjin 300071, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.affiliation: Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C The Rockefeller University, New York, New York 10065, USA.
authors.forename: Meike
authors.initials: M
authors.lastname: Dittmann
authors.affiliation: Program in Cellular and Molecular Medicine, Children's Hospital Boston, MA 02115, USA.|Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Alys
authors.initials: A
authors.lastname: Peisley
authors.affiliation: Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C The Rockefeller University, New York, New York 10065, USA.
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Hoffmann
authors.affiliation: Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C The Rockefeller University, New York, New York 10065, USA.
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Gilmore
authors.affiliation: Institut für Molekulare Medizin, Universitätsklinikum Bonn, 53127 Bonn, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmidt
authors.affiliation: Institut für Molekulare Medizin, Universitätsklinikum Bonn, 53127 Bonn, Germany.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schmidt-Burgk
authors.affiliation: Institut für Molekulare Medizin, Universitätsklinikum Bonn, 53127 Bonn, Germany.
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
authors.affiliation: Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C The Rockefeller University, New York, New York 10065, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.affiliation: Program in Cellular and Molecular Medicine, Children's Hospital Boston, MA 02115, USA.|Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sun
authors.initials: S
authors.lastname: Hur
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000998:Antiviral Agents / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D009690:Nucleic Acid Conformation; D010766:Phosphorylation; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014777:Virus Diseases / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D011971:Receptors, Immunologic; D051192:Receptors, Pattern Recognition; D014764:Viral Proteins; D016899:Interferon-beta; D000255:Adenosine Triphosphate; D019892:eIF-2 Kinase; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1