Vaccinia Virus Activation and Antagonism of Cytosolic DNA Sensing.
Vaccinia Virus Activation and Antagonism of Cytosolic DNA Sensing.
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DOI：
10.3389/fimmu.2020.568412
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发表时间：
2020
影响因子：
7.3
通讯作者：
Maluquer de Motes C
中科院分区：
文献类型：
--
作者：
El-Jesr M;Teir M;Maluquer de Motes C
细胞表达多种分子，旨在检测传入的病毒和感染。病毒感染的识别导致细胞因子、趋化因子和限制因子的产生，这些因子限制病毒复制并激活提供长期保护的适应性免疫应答。细胞溶质DNA的识别已经成为涉及感染、自身炎症和癌症免疫治疗的中心免疫传感机制。牛痘病毒（VACV）是痘病毒科的原型成员，并且是用于根除天花的疫苗。VACV作为疫苗载体具有巨大的潜力，目前正在开发几种减毒株以对抗传染病。此外，VACV已成为一种流行的溶瘤剂，由于其细胞毒性能力，即使在缺氧环境中。作为痘病毒，VACV是一种不寻常的病毒，其仅在感染细胞的细胞质中复制其大的DNA基因组。尽管产生大量的胞质DNA，VACV有效地抑制了随后的先天免疫反应，通过部署一个军火库的蛋白质的能力，使宿主的抗病毒信号，其中一些特异性靶向胞质DNA传感途径。其中一些策略在正痘病毒中是保守的，而另一些策略似乎是VACV所独有的。在这篇综述中，我们提供了一个概述的VACV复制周期，并讨论了我们的理解VACV如何诱导和拮抗先天性免疫激活通过胞质DNA传感途径的最新进展。还讨论了这些发现对基于VACV的疫苗和溶瘤药物合理设计的影响。
Cells express multiple molecules aimed at detecting incoming virus and infection. Recognition of virus infection leads to the production of cytokines, chemokines and restriction factors that limit virus replication and activate an adaptive immune response offering long-term protection. Recognition of cytosolic DNA has become a central immune sensing mechanism involved in infection, autoinflammation, and cancer immunotherapy. Vaccinia virus (VACV) is the prototypic member of the family Poxviridae and the vaccine used to eradicate smallpox. VACV harbors enormous potential as a vaccine vector and several attenuated strains are currently being developed against infectious diseases. In addition, VACV has emerged as a popular oncolytic agent due to its cytotoxic capacity even in hypoxic environments. As a poxvirus, VACV is an unusual virus that replicates its large DNA genome exclusively in the cytoplasm of infected cells. Despite producing large amounts of cytosolic DNA, VACV efficiently suppresses the subsequent innate immune response by deploying an arsenal of proteins with capacity to disable host antiviral signaling, some of which specifically target cytosolic DNA sensing pathways. Some of these strategies are conserved amongst orthopoxviruses, whereas others are seemingly unique to VACV. In this review we provide an overview of the VACV replicative cycle and discuss the recent advances on our understanding of how VACV induces and antagonizes innate immune activation via cytosolic DNA sensing pathways. The implications of these findings in the rational design of vaccines and oncolytics based on VACV are also discussed.