title: The cyclic GMP-AMP synthetase-STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly.
abstract: During viral replication, the innate immune response is induced through the recognition of viral replication intermediates by host factor(s). One of these host factors, cyclic GMP-AMP synthetase (cGAS), was recently reported to be involved in the recognition of viral DNA derived from DNA viruses. However, it is uncertain whether cGAS is involved in the recognition of hepatitis B virus (HBV), which is a hepatotropic DNA virus. In the present study, we demonstrated that HBV genome-derived double-stranded DNA induced the innate immune response through cGAS and its adaptor protein, stimulator of interferon genes (STING), in human hepatoma Li23 cells expressing high levels of cGAS. In addition, we demonstrated that HBV infection induced ISG56 through the cGAS-STING signaling pathway. This signaling pathway also showed an antiviral response towards HBV through the suppression of viral assembly. From these results, we conclude that the cGAS-STING signaling pathway is required for not only the innate immune response against HBV but also the suppression of HBV assembly. The cGAS-STING signaling pathway may thus be a novel target for anti-HBV strategies.
authors.affiliation: Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Dansako
authors.affiliation: Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: Youki
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Okumura
authors.affiliation: Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Satoh
authors.affiliation: Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
authors.affiliation: Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.|Department of Persistent and Oncogenic Viruses, Center for Chronic Viral Disease, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kato
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D006509:Hepatitis B / Q000276:immunology / Q000378:metabolism; D006515:Hepatitis B virus / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019065:Virus Assembly; D000099197:STING Protein
chemical_list: D000262:Adenylyl Cyclases; D006152:Cyclic GMP; D008565:Membrane Proteins; C532857:STING1 protein, human; D000099197:STING Protein
keywords: antiviral response; cGAS-STING signaling pathway; hepatitis B virus; innate immune response; viral assembly