The cyclic GMP-AMP synthetase-STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly
The cyclic GMP-AMP synthetase-STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly
复制标题
DOI：
10.1111/febs.13563
复制
发表时间：
2016-01-01
期刊：
影响因子：
5.4
通讯作者：
Kato, Nobuyuki
中科院分区：
文献类型：
--
作者：
Dansako, Hiromichi;Ueda, Youki;Kato, Nobuyuki
在病毒复制期间，通过宿主因子识别病毒复制中间体诱导先天免疫应答。这些宿主因子之一，环GMP-AMP合成酶（cGAS），最近被报道参与来自DNA病毒的病毒DNA的识别。然而，尚不确定cGAS是否参与识别B型肝炎病毒（HBV），HBV是一种嗜肝DNA病毒。在本研究中，我们证明了HBV基因组衍生的双链DNA通过cGAS及其衔接蛋白（干扰素基因刺激因子（STING））在表达高水平cGAS的人肝癌Li 23细胞中诱导先天性免疫应答。此外，我们证明了HBV感染通过cGAS-STING信号通路诱导ISG 56。该信号通路还显示出通过抑制病毒组装对HBV的抗病毒应答。从这些结果中，我们得出结论，cGAS-STING信号通路不仅是针对HBV的先天免疫应答所必需的，而且也是抑制HBV组装所必需的。因此，cGAS-STING信号通路可能是抗HBV策略的新靶标。
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.