title: Hepatitis B Virus-Induced Parkin-Dependent Recruitment of Linear Ubiquitin Assembly Complex (LUBAC) to Mitochondria and Attenuation of Innate Immunity.
abstract: Hepatitis B virus (HBV) suppresses innate immune signaling to establish persistent infection. Although HBV is a DNA virus, its pre-genomic RNA (pgRNA) can be sensed by RIG-I and activates MAVS to mediate interferon (IFN) λ synthesis. Despite of the activation of RIG-I-MAVS axis by pgRNA, the underlying mechanism explaining how HBV infection fails to induce interferon-αβ (IFN) synthesis remained uncharacterized. We demonstrate that HBV induced parkin is able to recruit the linear ubiquitin assembly complex (LUBAC) to mitochondria and abrogates IFN β synthesis. Parkin interacts with MAVS, accumulates unanchored linear polyubiquitin chains on MAVS via LUBAC, to disrupt MAVS signalosome and attenuate IRF3 activation. This study highlights the novel role of parkin in antiviral signaling which involves LUBAC being recruited to the mitochondria. These results provide avenues of investigations on the role of mitochondrial dynamics in innate immunity.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Mohsin
authors.initials: M
authors.lastname: Khan
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Gulam Hussain
authors.initials: GH
authors.lastname: Syed
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Seong-Jun
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Aleem
authors.initials: A
authors.lastname: Siddiqui
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006509:Hepatitis B / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering; D014162:Transfection; D025801:Ubiquitin / Q000276:immunology / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000276:immunology / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505371:MAVS protein, human; D034741:RNA, Small Interfering; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein