The battle between the innate immune cGAS-STING signaling pathway and human herpesvirus infection.
The battle between the innate immune cGAS-STING signaling pathway and human herpesvirus infection.
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DOI：
10.3389/fimmu.2023.1235590
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发表时间：
2023
影响因子：
7.3
通讯作者：
Huang, Cong
中科院分区：
文献类型：
--
作者：
Jin, Ximing;Wang, Wenjia;Zhao, Xinwei;Jiang, Wenhua;Shao, Qingqing;Chen, Zhuo;Huang, Cong
人类疱疹病毒（human herpesvirus，HHV）的发病率正在逐渐上升，并已影响到广泛的人群。HHV可导致肿瘤、新生儿畸形、性传播疾病等严重后果，对人类健康构成巨大威胁。cGAS-STING途径是最近发现的先天免疫模式识别受体之一。本文讨论了cGAS-STING通路在人类疾病中的作用，特别是在人类疱疹病毒感染中，以及强调这些病毒如何作用于该通路以逃避宿主免疫。此外，作者还提供了cGAS-STING途径调节剂的全面概述。通过关注基于cGAS-STING通路的小分子化合物，为抗病毒药物和疫苗的开发提出了新的靶点和概念，同时也为cGAS-STING通路相关疾病模型的研究提供了参考。HHV是一种双链DNA病毒，可以触发细胞内DNA传感器cGAS的激活，之后宿主细胞启动级联反应，最终分泌I型干扰素以限制病毒复制。同时，病毒蛋白可以与cGAS-STING途径中的各种分子相互作用。病毒可以通过抑制cGAS的酶活性和降低STING、TBK 1和IRF 3的磷酸化水平以及抑制干扰素基因活化来逃避免疫监视并维持其复制。cGAS-STING通路的激活剂和抑制剂已经在体外和体内产生了许多与cGAS/STING相关疾病模型有关的有前景的研究结果。然而，仍然缺乏已成功转化为临床应用的小分子调节剂，这是未来需要克服的障碍。
The incidence of human herpesvirus (HHVs) is gradually increasing and has affected a wide range of population. HHVs can result in serious consequences such as tumors, neonatal malformations, sexually transmitted diseases, as well as pose an immense threat to the human health. The cGAS-STING pathway is one of the innate immune pattern-recognition receptors discovered recently. This article discusses the role of the cGAS-STING pathway in human diseases, especially in human herpesvirus infections, as well as highlights how these viruses act on this pathway to evade the host immunity. Moreover, the author provides a comprehensive overview of modulators of the cGAS-STING pathway. By focusing on the small molecule compounds based on the cGAS-STING pathway, novel targets and concepts have been proposed for the development of antiviral drugs and vaccines, while also providing a reference for the investigation of disease models related to the cGAS-STING pathway. HHV is a double-stranded DNA virus that can trigger the activation of intracellular DNA sensor cGAS, after which the host cells initiate a cascade of reactions that culminate in the secretion of type I interferon to restrict the viral replication. Meanwhile, the viral protein can interact with various molecules in the cGAS-STING pathway. Viruses can evade immune surveillance and maintain their replication by inhibiting the enzyme activity of cGAS and reducing the phosphorylation levels of STING, TBK1 and IRF3 and suppressing the interferon gene activation. Activators and inhibitors of the cGAS-STING pathway have yielded numerous promising research findings in vitro and in vivo pertaining to cGAS/STING-related disease models. However, there remains a dearth of small molecule modulators that have been successfully translated into clinical applications, which serves as a hurdle to be overcome in the future.
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