title: Reversal of hepatitis B virus-induced systemic immune tolerance by intrinsic innate immune stimulation.
abstract: Systemic immune tolerance induced by chronic hepatitis B virus (HBV) infection is a significant question, but the mechanism of which remains unclear. In this mini-review, we summarize the impaired innate and adaptive immune responses involved in immune tolerance in chronic HBV infection. Furthermore, we delineate a novel dual functional small RNA to inhibit HBV replication and stimulate innate immunity against HBV, which proposed a promising immunotherapeutic intervention to interrupt HBV-induced immunotolerance. A mouse model of HBV persistence was established and used to observe the immune tolerant to HBV vaccination, the cell-intrinsic immune tolerance of which might be reversed by chemically synthesized dual functional small RNA (3p-hepatitis B Virus X gene [HBx]-small interfering RNA) in vitro experiments and by biologically constructed dual functional vector (single-stranded RNA-HBx- short hairpin RNA) in vivo experiment using HBV-carrier mice.
authors.affiliation: Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Han
authors.forename: Peixiang
authors.initials: P
authors.lastname: Lan
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology; D004195:Disease Models, Animal; D017325:Hepatitis B Vaccines / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D034741:RNA, Small Interfering / Q000502:physiology; D012367:RNA, Viral / Q000502:physiology; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors / Q000276:immunology; D014779:Virus Replication / Q000235:genetics
chemical_list: D017325:Hepatitis B Vaccines; D034741:RNA, Small Interfering; D012367:RNA, Viral; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
keywords: HBV; immune tolerance; intrinsic immunity