Herpes simplex virus infected cell protein 8 is required for viral inhibition of the cGAS pathway.
Herpes simplex virus infected cell protein 8 is required for viral inhibition of the cGAS pathway.
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DOI：
10.1016/j.virol.2023.05.002
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发表时间：
2023-05
期刊：
影响因子：
3.7
通讯作者：
N. Broekema;Max E. Mertens;Magdalena Angelova;M. H. Orzalli;H. Oh;D. Knipe
中科院分区：
文献类型：
--
作者：
N. Broekema;Max E. Mertens;Magdalena Angelova;M. H. Orzalli;H. Oh;D. Knipe
DNA病毒感染在细胞中触发抗病毒I型干扰素（IFN）应答，其抑制周围细胞的感染。因此，病毒已经进化出抑制IFN应答以进行有效复制的机制。细胞cGAS蛋白结合双链DNA并合成小分子cGAMP以启动DNA依赖性I型IFN产生。我们先前表明，与质粒DNA转染相比，在HSV-1感染期间cGAMP的产生相对较低。因此，我们假设HSV-1产生cGAS DNA传感途径的拮抗剂。在这项研究中，我们发现HSV-1 ICP 8蛋白是通过降低由双链DNA转染刺激的cGAMP水平来抑制cGAS途径所必需的。ICP 8单独抑制cGAMP反应，并且可以通过与DNA、cGAS或其他感染的细胞蛋白直接相互作用来抑制cGAS作用。我们的研究结果揭示了另一种cGAS抗病毒途径抑制剂，并强调了对抗IFN对有效病毒复制的重要性。
DNA virus infection triggers an antiviral type I interferon (IFN) response in cells that suppresses infection of surrounding cells. Consequently, viruses have evolved mechanisms to inhibit the IFN response for efficient replication. The cellular cGAS protein binds to double-stranded DNA and synthesizes the small molecule cGAMP to initiate DNA-dependent type I IFN production. We showed previously that cGAMP production is relatively low during HSV-1 infection compared to plasmid DNA transfection. Therefore, we hypothesized that HSV-1 produces antagonists of the cGAS DNA sensing pathway. In this study, we found that the HSV-1 ICP8 protein is required for viral inhibition of the cGAS pathway by reducing cGAMP levels stimulated by double-stranded DNA transfection. ICP8 alone inhibited the cGAMP response and may inhibit cGAS action by direct interaction with DNA, cGAS, or other infected cell proteins. Our results reveal another cGAS antiviral pathway inhibitor and highlight the importance of countering IFN for efficient viral replication.