The cyclic GMP-AMP synthetase-STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly

Hiromichi Dansako, Youki Ueda, Nobuaki Okumura, Shinya Satoh, Masaya Sugiyama, Masashi Mizokami, Masanori Ikeda, Nobuyuki Kato

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)144-156
Number of pages13
JournalFEBS Journal
Volume283
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

Fingerprint

GMP synthase (glutamine-hydrolyzing)
Virus Assembly
Ligases
Viruses
Innate Immunity
Hepatitis B virus
Interferons
Genes
DNA Viruses
DNA
Viral DNA
Virus Diseases
cyclic guanosine monophosphate-adenosine monophosphate
Antiviral Agents
Hepatocellular Carcinoma

Keywords

  • antiviral response
  • cGAS-STING signaling pathway
  • hepatitis B virus
  • innate immune response
  • viral assembly

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

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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.",
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AU - Dansako, Hiromichi

AU - Ueda, Youki

AU - Okumura, Nobuaki

AU - Satoh, Shinya

AU - Sugiyama, Masaya

AU - Mizokami, Masashi

AU - Ikeda, Masanori

AU - Kato, Nobuyuki

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