为了确定对冠状病毒感染至关重要的宿主因素，研究人员对SARS-CoV-2和人冠状病毒229E进行了全基因组功能遗传筛选。这些筛选发现了病毒特异性以及共有的宿主因子，包括TMEM41B和3型PI3K。研究人员发现SARS-CoV-2需要溶酶体蛋白TMEM106B才能感染人细胞系和原代肺细胞。TMEM106B过表达增强了SARS-CoV-2感染以及伪病毒感染，从而表明在病毒进入中起作用。此外，来自COVID-19患者气道细胞的单细胞RNA测序证明TMEM106B表达与SARS-CoV-2感染相关。
这项研究揭示了冠状病毒宿主因素，可利用这些因素来开发抗SARS-CoV-2感染或未来人畜共患冠状病毒爆发的药物。
附：英文原文
Title: Genome-wide CRISPR screening identifies TMEM106B as a proviral host factor for SARS-CoV-2
Author: Jim Baggen, Leentje Persoons, Els Vanstreels, Sander Jansen, Dominique Van Looveren, Bram Boeckx, Vincent Geudens, Julie De Man, Dirk Jochmans, Joost Wauters, Els Wauters, Bart M. Vanaudenaerde, Diether Lambrechts, Johan Neyts, Kai Dallmeier, Hendrik Jan Thibaut, Maarten Jacquemyn, Piet Maes, Dirk Daelemans
Issue&Volume: 2021-03-08
Abstract: The ongoing COVID-19 pandemic has caused a global economic and health crisis. To identify host factors essential for coronavirus infection, we performed genome-wide functional genetic screens with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human coronavirus 229E. These screens uncovered virus-specific as well as shared host factors, including TMEM41B and PI3K type 3. We discovered that SARS-CoV-2 requires the lysosomal protein TMEM106B to infect human cell lines and primary lung cells. TMEM106B overexpression enhanced SARS-CoV-2 infection as well as pseudovirus infection, suggesting a role in viral entry. Furthermore, single-cell RNA-sequencing of airway cells from patients with COVID-19 demonstrated that TMEM106B expression correlates with SARS-CoV-2 infection. The present study uncovered a collection of coronavirus host factors that may be exploited to develop drugs against SARS-CoV-2 infection or future zoonotic coronavirus outbreaks.
DOI: 10.1038/s41588-021-00805-2
Source: https://www.nature.com/articles/s41588-021-00805-2
Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
