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

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 dsDNA induced the innate immune response through cGAS and its adaptor protein, 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.

This is the peer reviewed version of the following article: Hiromichi Dansako, Youki Ueda, Nobuaki Okumura, Shinya Satoh, Masaya Sugiyama, Masashi Mizokami, Masanori Ikeda and Nobuyuki Kato The cyclic GMP-AMP synthetase-STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly FEBS Journal, which has been published in final form at http://dx.doi.org/10.1111/febs.13563. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.