title: Hepatitis B virus inhibits intrinsic RIG-I and RIG-G immune signaling via inducing miR146a.
abstract: Previous studies showed that hepatitis B virus (HBV), as a latency invader, attenuated host anti-viral immune responses. miRNAs were shown to be involved in HBV infection and HBV-related diseases, however, the precise role of miRNAs in HBV-mediated immunosuppression remains unclear. Here, we observed that down-regulated RIG-I like receptors might be one critical mechanism of HBV-induced suppression of type I IFN transcription in both HBV(+) hepatoma cell lines and liver cancer tissues. Then, miR146a was demonstrated to negatively regulate the expression of RIG-I-like receptors by directly targeting both RIG-I and RIG-G. Further investigation showed that antagonizing miR146a by anti-sense inhibitors or sponge approach accelerated HBV clearance and reduced HBV load both in vitro and in a HBV-carrying mouse model. Therefore, our findings indicated that HBV-induced miR146a attenuates cell-intrinsic anti-viral innate immunity through targeting RIG-I and RIG-G, and silencing miR146a might be an effective target to reverse HBV-induced immune suppression.
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, China.
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Han
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, China.
authors.forename: Chenhe
authors.initials: C
authors.lastname: Su
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qu
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Xu
authors.affiliation: Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.|Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
mesh_terms: D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D004195:Disease Models, Animal; D006509:Hepatitis B / Q000276:immunology / Q000821:virology; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D035683:MicroRNAs; D011971:Receptors, Immunologic; D015398:Signal Transduction
chemical_list: C116468:IFIT3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D011971:Receptors, Immunologic; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58