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TMEM41B is a pan-flavivirus host factor
bioRxiv - Molecular Biology Pub Date : 2020-10-11 , DOI: 10.1101/2020.10.09.334128
H.-Heinrich Hoffmann , William M Schneider , Kathryn Rozen-Gagnon , Linde A Miles , Felix Schuster , Brandon Razooky , Eliana Jacobson , Xianfang Wu , Soon Yi , Charles M Rudin , Margaret R MacDonald , Laura K McMullan , John T Poirier , Charles M Rice

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 (SNPs) present at nearly twenty percent in East Asian populations reduce flavivirus infection. Based on our mechanistic studies we hypothesize 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病毒通过被叮咬的蚊子和tick虫叮咬传播,并经常引起疾病暴发。为了鉴定黄病毒感染所需的宿主因子,我们进行了全基因组功能丧失的CRISPR-Cas9筛选。基于这些结果,我们集中精力确定了TMEM41B和VMP1在病毒复制周期中所起的作用。我们对TMEM41B的机理研究表明,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也需要TMEM41B进行感染。值得注意的是,东亚人口中近20%的单核苷酸多态性(SNP)减少了黄病毒感染。
更新日期:2020-10-12
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