title: MITA/STING and Its Alternative Splicing Isoform MRP Restrict Hepatitis B Virus Replication.
abstract: An efficient clearance of hepatitis B virus (HBV) requires the coordinated work of both the innate and adaptive immune responses. MITA/STING, an adapter protein of the innate immune signaling pathways, plays a key role in regulating innate and adaptive immune responses to DNA virus infection. Previously, we identified an alternatively spliced isoform of MITA/STING, called MITA-related protein (MRP), and found that MRP could specifically block MITA-mediated interferon (IFN) induction while retaining the ability to activate NF-κB. Here, we asked whether MITA/STING and MRP were able to control the HBV replication. Both MITA/STING and MRP significantly inhibited HBV replication in vitro. MITA overexpression stimulated IRF3-IFN pathway; while MRP overexpression activated NF-κB pathway, suggesting these two isoforms may inhibit HBV replication through different ways. Using a hydrodynamic injection (HI) mouse model, we found that HBV replication was reduced following MITA/STING and MRP expression vectors in mice and was enhanced by the knockout of MITA/STING (MITA/STING-/-). The HBV specific humoral and CD8+ T cell responses were impaired in MITA/STING deficient mice, suggesting the participation of MITA/STING in the initiation of host adaptive immune responses. In summary, our data suggest that MITA/STING and MRP contribute to HBV control via modulation of the innate and adaptive responses.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Shuhui
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Kaitao
authors.initials: K
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: He
authors.initials: H
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Xianwen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Chunchen
authors.initials: C
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Jizheng
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Yanyi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Rongjuan
authors.initials: R
authors.lastname: Pei
mesh_terms: D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014779:Virus Replication / Q000235:genetics / Q000502:physiology; D000099197:STING Protein
chemical_list: D008565:Membrane Proteins; D020033:Protein Isoforms; C532857:STING1 protein, human; D000099197:STING Protein