title: A MAVS/TICAM-1-independent interferon-inducing pathway contributes to regulation of hepatitis B virus replication in the mouse hydrodynamic injection model.
abstract: Toll-like receptors (TLRs) and cytoplasmic RNA sensors have been reported to be involved in the regulation of hepatitis B virus (HBV) replication, but remain controversial due to the lack of a natural infectious model. Our current study sets out to characterize aspects of the role of the innate immune system in eliminating HBV using hydrodynamic-based injection of HBV replicative plasmid and knockout mice deficient in specific pathways of the innate system. The evidence indicated that viral replication was not affected by MAVS or TICAM-1 knockout, but absence of interferon regulatory factor 3 (IRF-3) and IRF-7 transcription factors, as well as the interferon (IFN) receptor, had an adverse effect on the inhibition of HBV replication, demonstrating the dispensability of MAVS and TICAM-1 pathways in the early innate response against HBV. Myd88(-/-) mice did not have a significant increase in the initial viremia, but substantial viral antigen persisted in the mice sera, a response similar to Rag2(-/-) mice, suggesting that the MyD88-dependent pathway participated in evoking an adaptive immune response against the clearance of intrahepatic HBV. Taken together, we show that the RNA-sensing pathways do not participate in the regulation of HBV replication in a mouse model; meanwhile MyD88 is implicated in the HBV clearance.
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Chean Ring
authors.initials: CR
authors.lastname: Leong
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Oshiumi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Okamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Azuma
authors.forename: Hiromi
authors.initials: H
authors.lastname: Takaki
authors.forename: Misako
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Seya
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology*; D006511:Hepatitis B Antigens / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000502:physiology*; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D006511:Hepatitis B Antigens; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D053594:Myeloid Differentiation Factor 88; C512612:MAVS protein, mouse; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse