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TMEM41B Is a Pan-flavivirus Host Factor
Cell ( IF 64.5 ) Pub Date : 2020-12-09 , DOI: 10.1016/j.cell.2020.12.005
H-Heinrich Hoffmann 1 , William M Schneider 1 , Kathryn Rozen-Gagnon 1 , Linde A Miles 2 , Felix Schuster 3 , Brandon Razooky 1 , Eliana Jacobson 1 , Xianfang Wu 1 , Soon Yi 1 , Charles M Rudin 4 , Margaret R MacDonald 1 , Laura K McMullan 5 , John T Poirier 6 , Charles M Rice 1
Affiliation  

Flaviviruses pose a constant threat to human health. These RNA viruses are transmitted by the bite of infected mosquitoes and ticks and regularly cause outbreaks. To identify host factors required for flavivirus infection, we performed full-genome loss of function CRISPR-Cas9 screens. Based on these results, we focused our efforts on characterizing the roles that TMEM41B and VMP1 play in the virus replication cycle. Our mechanistic studies on TMEM41B revealed that all members of the Flaviviridae family that we tested require TMEM41B. We tested 12 additional virus families and found that SARS-CoV-2 of the Coronaviridae also required TMEM41B for infection. Remarkably, single nucleotide polymorphisms present at nearly 20% in East Asian populations reduce flavivirus infection. Based on our mechanistic studies, we propose that TMEM41B is recruited to flavivirus RNA replication complexes to facilitate membrane curvature, which creates a protected environment for viral genome replication.



中文翻译:

TMEM41B 是泛黄病毒宿主因子

黄病毒对人类健康构成持续威胁。这些 RNA 病毒通过受感染的蚊子和蜱虫叮咬传播,并经常引起疫情爆发。为了确定黄病毒感染所需的宿主因子,我们进行了全基因组功能缺失 CRISPR-Cas9 筛选。基于这些结果,我们重点研究了 TMEM41B 和 VMP1 在病毒复制周期中所扮演的角色。我们对 TMEM41B 的机制研究表明,我们测试的黄病毒科的所有成员都需要 TMEM41B。我们测试了另外 12 个病毒家族,发现冠状病毒科的 SARS-CoV-2还需要 TMEM41B 来进行感染。值得注意的是,东亚人群中近 20% 的单核苷酸多态性减少了黄病毒感染。根据我们的机制研究,我们建议将 TMEM41B 招募到黄病毒 RNA 复制复合物中以促进膜弯曲,从而为病毒基因组复制创造一个受保护的环境。

更新日期:2021-01-07
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