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研究实现SARS-CoV-2和冠状病毒宿主因子网络的基因组规模鉴定
作者:小柯机器人 发布时间:2020/12/12 19:49:42

美国纽约大学John T. Poirier、洛克菲勒大学Charles M. Rice等研究人员合作,实现SARS-CoV-2和冠状病毒宿主因子网络的基因组规模鉴定。相关论文于2020年12月9日在线发表于国际学术期刊《细胞》。

研究人员表示,COVID-19大流行已经在全球夺走了超过100万人的生命。病原体SARS-CoV-2是冠状病毒科的病毒成员,可导致严重程度不同的呼吸道感染。在SARS-CoV-2和相关冠状病毒生命周期中选择的细胞宿主因子和途径仍然不清楚。

为了解决这个难题,研究人员在SARS-CoV-2和三种季节性冠状病毒(HCoV-OC43、HCoV-NL63和HCoV-229E)感染期间进行了基因组规模的CRISPR基因敲除筛选。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素和途径,包括糖胺聚糖生物合成、SREBP信号传导、BMP信号传导和糖基磷脂酰肌醇生物合成,以及对几种未知蛋白质的需要。

研究人员发现对于SARS-CoV-2和三种季节性冠状病毒感染所必须的含VTT结构域蛋白TMEM41B。这个人类冠状病毒科宿主因子筛选是一个丰富的资源,可为当前的COVID-19和将来的冠状病毒大流行开发新的治疗策略。

附:英文原文

Title: Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks

Author: William M. Schneider, Joseph M. Luna, H.-Heinrich Hoffmann, Francisco J. Sanchez-Rivera, Andrew A. Leal, Alison W. Ashbrook, Jeremie Le Pen, Inna Ricardo-Lax, Eleftherios Michailidis, Avery Peace, Ansgar F. Stenzel, Scott W. Lowe, Margaret R. MacDonald, Charles M. Rice, John T. Poirier

Issue&Volume: 2020-12-09

Abstract: The COVID-19 pandemic has claimed the lives of over one million people worldwide. The causative agent, 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, SREBP signaling, BMP signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VTT-domain containing protein TMEM41B for infection by SARS-CoV-2 and three seasonal coronaviruses. This human Coronaviridae host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus pandemics.

DOI: 10.1016/j.cell.2020.12.006

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31676-7

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/