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登革热病毒感染期间的附带损害:通过cGAS理解DNA

Collateral Damage during Dengue Virus Infection: Making Sense of DNA by cGAS.

作者信息

Aguirre Sebastian, Fernandez-Sesma Ana

机构信息

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

出版信息

J Virol. 2017 Jun 26;91(14). doi: 10.1128/JVI.01081-16. Print 2017 Jul 15.

Abstract

Early sensing of viral components or infection-induced tissue damage is a prerequisite for the successful control of pathogenic viruses by the host innate immune system. Recent results from our laboratory show how immune cells use the DNA-sensing machinery to detect intracellular damage generated early during infection by an RNA virus, namely, dengue virus (DENV). Conversely, we found that DENV can efficiently dismantle this sensing mechanism by targeting the cyclic GMP-AMP synthase (cGAS) and the stimulator of interferon (IFN) genes (STING), two crucial host factors involved in DNA detection and type I IFN production. These findings highlight the relevance of the DNA-sensing mechanism in the detection and control of infections by RNA viruses. In this review, we discuss how DENV modulates the innate immune DNA-sensing pathway, activated in the context of cellular damage during infection.

摘要

宿主先天免疫系统成功控制致病性病毒的一个先决条件是对病毒成分或感染诱导的组织损伤进行早期感知。我们实验室最近的研究结果表明,免疫细胞如何利用DNA感知机制来检测RNA病毒(即登革病毒,DENV)感染早期产生的细胞内损伤。相反,我们发现DENV可以通过靶向环磷酸鸟苷-磷酸腺苷合酶(cGAS)和干扰素(IFN)基因刺激物(STING)来有效破坏这种感知机制,这两个关键的宿主因子参与DNA检测和I型IFN的产生。这些发现突出了DNA感知机制在检测和控制RNA病毒感染中的相关性。在这篇综述中,我们讨论了DENV如何调节在感染期间细胞损伤情况下被激活的先天免疫DNA感知途径。

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