Shiftless, a Critical Piece of the Innate Immune Response to Viral Infection.

Shiftless, a Critical Piece of the Innate Immune Response to Viral Infection.
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DOI:
10.3390/v14061338
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发表时间:
2022-06-20
期刊:
Viruses
影响因子:
--
通讯作者:
--
中科院分区:
其他
文献类型:
--
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自2016年首次鉴定以来,干扰素刺激基因Shiftless (SHFL)已被证明是对病毒感染的先天免疫反应的关键部分。SHFL的表达严格限制了多种DNA、RNA和逆转录病毒的复制,这些病毒具有不同于其他病毒的不同机制。这些抑制策略包括在病毒感染期间对病毒RNA稳定性、翻译甚至RNA颗粒形成的负调控。更令人惊讶的是,SHFL是第一个被发现直接抑制-1程序核糖体移码活性的人类蛋白质,移码是一种翻译重编码策略,几乎在所有生命领域和几种人类病毒中都被使用。最近的文献表明,SHFL的表达在小鼠模型中也显著影响病毒的发病机制,突出了其在体内的功效。为了帮助调和SHFL限制病毒复制的许多机制,我们在这里全面回顾了这种复杂的ISG,它对病毒RNA命运的影响,以及它在病毒-宿主军备竞赛中控制细胞的功能的含义。
Since its initial characterization in 2016, the interferon stimulated gene Shiftless (SHFL) has proven to be a critical piece of the innate immune response to viral infection. SHFL expression stringently restricts the replication of multiple DNA, RNA, and retroviruses with an extraordinary diversity of mechanisms that differ from one virus to the next. These inhibitory strategies include the negative regulation of viral RNA stability, translation, and even the manipulation of RNA granule formation during viral infection. Even more surprisingly, SHFL is the first human protein found to directly inhibit the activity of the -1 programmed ribosomal frameshift, a translation recoding strategy utilized across nearly all domains of life and several human viruses. Recent literature has shown that SHFL expression also significantly impacts viral pathogenesis in mouse models, highlighting its in vivo efficacy. To help reconcile the many mechanisms by which SHFL restricts viral replication, we provide here a comprehensive review of this complex ISG, its influence over viral RNA fate, and the implications of its functions on the virus-host arms race for control of the cell.
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