Discovering antiviral restriction factors and pathways using genetic screens.

Discovering antiviral restriction factors and pathways using genetic screens.
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DOI:
10.1099/jgv.0.001603
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发表时间:
2021-05
期刊:
The Journal of general virology
影响因子:
--
通讯作者:
Hughes DJ
Hughes DJ
中科院分区:
其他
文献类型:
--
作者:
Jones CE;Tan WS;Grey F;Hughes DJ

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病毒感染激活强大的干扰素(IFN)反应,诱导数百个IFN刺激基因(ISG)的表达。这种广泛的反应的主要作用是为病毒复制创造一个不利的环境,并限制传播;然而,解开这种大规模反应的生物后果是复杂的。除了看似高度冗余之外,通常还需要多个ISG组合使用以限制感染,因为单个ISG通常具有低至中等的抗病毒活性。此外,对于给定的病毒,什么ISG或ISG的组合是抗病毒的通常是未知的。由于这些原因,并且由于许多ISG的功能尚未探索,因此全基因组方法很好地用于研究这种应答的哪些方面导致适当的病毒特异性表型。本文综述了近年来用于研究宿主防御机制的筛选方法,包括成簇规则间隔短回文重复序列/CRISPR相关蛋白9(CRISPR/Cas9)、ISG表达文库和RNA干扰(RNAi)技术。
Viral infections activate the powerful interferon (IFN) response that induces the expression of several hundred IFN stimulated genes (ISGs). The principal role of this extensive response is to create an unfavourable environment for virus replication and to limit spread; however, untangling the biological consequences of this large response is complicated. In addition to a seemingly high degree of redundancy, several ISGs are usually required in combination to limit infection as individual ISGs often have low to moderate antiviral activity. Furthermore, what ISG or combination of ISGs are antiviral for a given virus is usually not known. For these reasons, and since the function(s) of many ISGs remains unexplored, genome-wide approaches are well placed to investigate what aspects of this response result in an appropriate, virus-specific phenotype. This review discusses the advances screening approaches have provided for the study of host defence mechanisms, including clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9), ISG expression libraries and RNA interference (RNAi) technologies.
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