Functional landscape of SARS-CoV-2 cellular restriction.
Functional landscape of SARS-CoV-2 cellular restriction.
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DOI：
10.1016/j.molcel.2021.04.008
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发表时间：
2021-06-17
期刊：
影响因子：
16
通讯作者：
Chanda SK
中科院分区：
文献类型：
--
作者：
Martin-Sancho L;Lewinski MK;Pache L;Stoneham CA;Yin X;Becker ME;Pratt D;Churas C;Rosenthal SB;Liu S;Weston S;De Jesus PD;O'Neill AM;Gounder AP;Nguyen C;Pu Y;Curry HM;Oom AL;Miorin L;Rodriguez-Frandsen A;Zheng F;Wu C;Xiong Y;Urbanowski M;Shaw ML;Chang MW;Benner C;Hope TJ;Frieman MB;García-Sastre A;Ideker T;Hultquist JF;Guatelli J;Chanda SK
对严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染的干扰素（IFN）缺乏反应被认为是2019年严重冠状病毒病（COVID-19）的决定因素。为了确定控制SARS-CoV-2感染的IFN控制的分子效应器，我们进行了大规模的功能获得性分析，评估了人IFN刺激基因（ISG）对病毒复制的影响。发现ISG的有限子集控制病毒感染，包括抑制病毒进入的内体因子、抑制病毒RNA合成的RNA结合蛋白和抑制病毒组装/排出的内质网（ER）/高尔基体驻留ISG的高度富集簇。其中包括广谱抗病毒ISG和8个特异性抑制SARS-CoV-2和SARS-CoV-1复制的ISG。广泛作用的ISG之一是BST 2/tetherin，它阻碍病毒释放，并被SARS-CoV-2 Orf 7a蛋白拮抗。总体而言，这些数据阐明了SARS-CoV-2/SARS-CoV-1感染的先天免疫控制基础的一组ISG，这将有助于理解影响疾病严重程度的宿主决定因素，并为COVID-19提供潜在的治疗策略。对SARS-CoV-2感染的干扰素应答不足与严重的COVID-19有关。马丁-桑乔等人利用功能获得筛选来鉴定干扰素刺激的效应物，其控制对SARS-CoV-2的先天免疫应答。这些因素可能是严重COVID-19遗传易感性的基础，并可作为开发抗病毒疗法的候选因素。
A deficient interferon (IFN) response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated as a determinant of severe coronavirus disease 2019 (COVID-19). To identify the molecular effectors that govern IFN control of SARS-CoV-2 infection, we conducted a large-scale gain-of-function analysis that evaluated the impact of human IFN-stimulated genes (ISGs) on viral replication. A limited subset of ISGs were found to control viral infection, including endosomal factors inhibiting viral entry, RNA binding proteins suppressing viral RNA synthesis, and a highly enriched cluster of endoplasmic reticulum (ER)/Golgi-resident ISGs inhibiting viral assembly/egress. These included broad-acting antiviral ISGs and eight ISGs that specifically inhibited SARS-CoV-2 and SARS-CoV-1 replication. Among the broad-acting ISGs was BST2/tetherin, which impeded viral release and is antagonized by SARS-CoV-2 Orf7a protein. Overall, these data illuminate a set of ISGs that underlie innate immune control of SARS-CoV-2/SARS-CoV-1 infection, which will facilitate the understanding of host determinants that impact disease severity and offer potential therapeutic strategies for COVID-19. Deficient interferon responses to SARS-CoV-2 infection have been associated with severe COVID-19. Martin-Sancho et al. utilized a gain-of-function screen to identify interferon-stimulated effectors that govern innate immune responses to SARS-CoV-2. These factors could underlie genetic predisposition to severe COVID-19 and can serve as candidates for development of antiviral therapies.
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影响因子：
64.5
作者：
Hou, Yixuan J.;Okuda, Kenichi;Baric, Ralph S.
通讯作者：
Baric, Ralph S.
病毒逃避干扰素的十种策略。
影响因子：
30.3
作者：
García-Sastre A
通讯作者：
García-Sastre A
影响因子：
14.8
作者：
Kozakov D;Hall DR;Xia B;Porter KA;Padhorny D;Yueh C;Beglov D;Vajda S
通讯作者：
Vajda S
影响因子：
56.9
作者：
Lamers, Mart M.;Beumer, Joep;Clevers, Hans
通讯作者：
Clevers, Hans
DOI：
10.1073/pnas.0911679106
发表时间：
2009-12-01
影响因子：
11.1
作者：
Hinson, Ella R.;Cresswell, Peter
通讯作者：
Cresswell, Peter