Small Hero with Great Powers: Vaccinia Virus E3 Protein and Evasion of the Type I IFN Response.

Small Hero with Great Powers: Vaccinia Virus E3 Protein and Evasion of the Type I IFN Response.
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具有强大力量的小英雄:疫苗病毒E3蛋白和I型IFN反应的逃避。

DOI:
10.3390/biomedicines10020235
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发表时间:
2022-01-22
期刊:
影响因子:
4.7
通讯作者:
Jacobs BL
Jacobs BL
中科院分区:
工程技术3区
文献类型:
--
作者:
Szczerba M;Subramanian S;Trainor K;McCaughan M;Kibler KV;Jacobs BL

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痘病毒科已经开发了大量的策略来逃避先天性和适应性免疫。本文主要介绍了由E3 L基因编码的牛痘病毒E3蛋白。E3存在于脊索痘病毒亚科(除了禽痘病毒和传染性软疣病毒)中,并对先天免疫系统显示多效性作用。最初的研究发现E3是一种双链RNA(dsRNA)结合蛋白(通过其C末端),能够抑制依赖于RNA的蛋白激酶(PKR)和2′5′-寡腺苷酸合成酶(OAS)/RNase L途径的激活,使E3成为一种对抗I型干扰素(IFN)系统的蛋白。近年来,E3的N-末端突变体不能与Z-型核酸结合,已被证明可诱导细胞死亡途径坏死性凋亡。该途径依赖于宿主IFN诱导的Z-DNA结合蛋白1(ZBP 1);全长E3能够抑制ZBP 1介导的坏死性凋亡。与被鉴定为Z-RNA的结合已经成为抵消I型IFN系统的新机制,并且拓宽了我们对针对病毒感染的先天免疫的理解。本文概述了导致我们了解的牛痘病毒E3蛋白的功能及其参与病毒的发病机制的研究。此外,还提供了其他病毒系统的简短总结。
Poxviridae have developed a plethora of strategies to evade innate and adaptive immunity. In this review, we focused on the vaccinia virus E3 protein, encoded by the E3L gene. E3 is present within the Chordopoxvirinae subfamily (with the exception of the avipoxviruses and molluscum contagiosum virus) and displays pleiotropic effects on the innate immune system. Initial studies identified E3 as a double-stranded RNA (dsRNA)-binding protein (through its C terminus), able to inhibit the activation of protein kinase dependent on RNA (PKR) and the 2′5′-oligoadenylate synthetase (OAS)/RNase L pathway, rendering E3 a protein counteracting the type I interferon (IFN) system. In recent years, N-terminal mutants of E3 unable to bind to Z-form nucleic acids have been shown to induce the cellular death pathway necroptosis. This pathway was dependent on host IFN-inducible Z-DNA-binding protein 1 (ZBP1); full-length E3 is able to inhibit ZBP1-mediated necroptosis. Binding to what was identified as Z-RNA has emerged as a novel mechanism of counteracting the type I IFN system and has broadened our understanding of innate immunity against viral infections. This article gives an overview of the studies leading to our understanding of the vaccinia virus E3 protein function and its involvement in viral pathogenesis. Furthermore, a short summary of other viral systems is provided.
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