Hepatitis B Virus-Induced Parkin-Dependent Recruitment of Linear Ubiquitin Assembly Complex (LUBAC) to Mitochondria and Attenuation of Innate Immunity

PLoS Pathogens

Aleem Siddiqui¹  Seong-Jun Kim¹  Mohsin Khan¹  Gulam Hussain Syed¹ 

[1] Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, California, United States of America

关键词: Mitochondria;    Immunoprecipitation;    Hepatitis B virus;    Transfection;    Interferons;    Phosphorylation;    Antiviral immune response;    Ubiquitination;   

DOI  :  10.1371/journal.ppat.1005693

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY