title: Inhibition of RIG-I-mediated signaling by Kaposi's sarcoma-associated herpesvirus-encoded deubiquitinase ORF64.
abstract: Virus infection triggers interferon (IFN)-mediated innate immune defenses in part through viral nucleic acid interactions. However, the immune recognition mechanisms by which the host identifies incoming DNA viruses are still elusive. Here, we show that increased levels of Kaposi's sarcoma-associated herpesvirus (KSHV) persistency are observed in retinoic acid-inducible gene I (RIG-I)-deficient cells and that KSHV ORF64, a tegument protein with deubiqutinase (DUB) activity, suppresses RIG-I-mediated IFN signaling by reducing the ubiquitination of RIG-I, crucial for its activation. This study suggests that RIG-I plays a potential role in sensing KSHV infection and that KSHV ORF64 DUB counteracts RIG-I signaling.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Inn
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Jessica Y
authors.initials: JY
authors.lastname: Rathbun
authors.forename: Lai-Yee
authors.initials: LY
authors.lastname: Wong
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Toth
authors.forename: Keigo
authors.initials: K
authors.lastname: Machida
authors.forename: Jing-Hsiung James
authors.initials: JH
authors.lastname: Ou
authors.forename: Jae U
authors.initials: JU
authors.lastname: Jung
mesh_terms: D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors* / Q000276:immunology; D010450:Endopeptidases / Q000378:metabolism*; D019288:Herpesvirus 8, Human / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D057131:Immune Evasion; D007372:Interferons / Q000037:antagonists & inhibitors / Q000276:immunology; D011971:Receptors, Immunologic; D015398:Signal Transduction; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D011971:Receptors, Immunologic; D014764:Viral Proteins; D007372:Interferons; D010450:Endopeptidases; C091939:ubiquitin isopeptidase; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases