Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks.
Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks.
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DOI：
10.1016/j.cell.2020.12.006
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发表时间：
2021-01-07
期刊：
影响因子：
64.5
通讯作者：
Poirier JT
中科院分区：
文献类型：
--
作者：
Schneider WM;Luna JM;Hoffmann HH;Sánchez-Rivera FJ;Leal AA;Ashbrook AW;Le Pen J;Ricardo-Lax I;Michailidis E;Peace A;Stenzel AF;Lowe SW;MacDonald MR;Rice CM;Poirier JT
2019冠状病毒病（COVID-19）大流行已夺去全球超过一百万人的生命。病原体，严重急性呼吸综合征冠状病毒2（SARS-CoV-2），是冠状病毒科病毒的成员，可引起不同严重程度的呼吸道感染。在SARS-CoV-2和相关冠状病毒生命周期中，细胞宿主因子和途径仍然不清楚。为了解决这一差距，我们在SARS-CoV-2和三种季节性冠状病毒（HCoV-OC 43，HCoV-NL 63和HCoV-229 E）感染期间进行了基因组规模的CRISPR敲除筛选。这些筛选发现了具有泛冠状病毒和病毒特异性功能作用的宿主因子和途径，包括对糖胺聚糖生物合成、固醇调节元件结合蛋白（SREBP）信号传导、骨形态发生蛋白（BMP）信号传导和糖基磷脂酰肌醇生物合成的主要依赖性，以及对几种表征不佳的蛋白质的需求。我们确定了SARS-CoV-2和三种季节性冠状病毒感染对含有VMP 1、TMEM 41和TMEM 64（VTT）结构域的蛋白跨膜蛋白41 B（TMEM 41 B）的绝对需求。这本人类冠状病毒宿主因子纲要代表了为急性COVID-19和潜在的未来冠状病毒大流行开发新治疗策略的丰富资源。Schneider等人对SARS-CoV-2和三种季节性冠状病毒进行了平行的全基因组CRISPR敲除筛选，以确定泛冠状病毒和病毒特异性宿主因子的要求。他们确定了这四种病毒所需的宿主因子的互连网络，并验证了TMEM 41 B是冠状病毒生命周期中进入后步骤所需的泛冠状病毒宿主因子。
The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of over one million people worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a member of the Coronaviridae family of viruses that can cause respiratory infections of varying severity. The cellular host factors and pathways co-opted during SARS-CoV-2 and related coronavirus life cycles remain ill defined. To address this gap, we performed genome-scale CRISPR knockout screens during infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E). These screens uncovered host factors and pathways with pan-coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, sterol regulatory element-binding protein (SREBP) signaling, bone morphogenetic protein (BMP) signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VMP1, TMEM41, and TMEM64 (VTT) domain-containing protein transmembrane protein 41B (TMEM41B) for infection by SARS-CoV-2 and three seasonal coronaviruses. This human coronavirus host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus pandemics. Schneider et al. conducted parallel genome-wide CRISPR knockout screens with SARS-CoV-2 and three seasonal coronaviruses to identify pan-coronavirus and virus-specific host factor requirements. They identified an interconnected network of host factors required by these four viruses and validated TMEM41B as a pan-coronavirus host factor required for a post-entry step in the coronavirus life cycle.
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