tetano
Editor, Senior Moderator
PLoS Pathog
. 2021 Dec 6;17(12):e1010113.
doi: 10.1371/journal.ppat.1010113. Online ahead of print.
Genome-scale CRISPR screen identifies TMEM41B as a multi-function host factor required for coronavirus replication
Limeng Sun[SUP] 1 2 [/SUP], Changzhi Zhao[SUP] 3 [/SUP], Zhen Fu[SUP] 1 2 [/SUP], Yanan Fu[SUP] 1 2 [/SUP], Zhelin Su[SUP] 1 2 [/SUP], Yangyang Li[SUP] 4 [/SUP], Yuan Zhou[SUP] 3 [/SUP], Yubei Tan[SUP] 1 2 [/SUP], Jingjin Li[SUP] 3 [/SUP], Yixin Xiang[SUP] 1 2 [/SUP], Xiongwei Nie[SUP] 3 [/SUP], Jinfu Zhang[SUP] 3 [/SUP], Fei Liu[SUP] 4 [/SUP], Shuhong Zhao[SUP] 3 5 [/SUP], Shengsong Xie[SUP] 3 [/SUP], Peng Guiqing[SUP] 1 2 [/SUP]
Affiliations
Abstract
Emerging coronaviruses (CoVs) pose a severe threat to human and animal health worldwide. To identify host factors required for CoV infection, we used α-CoV transmissible gastroenteritis virus (TGEV) as a model for genome-scale CRISPR knockout (KO) screening. Transmembrane protein 41B (TMEM41B) was found to be a bona fide host factor involved in infection by CoV and three additional virus families. We found that TMEM41B is critical for the internalization and early-stage replication of TGEV. Notably, our results also showed that cells lacking TMEM41B are unable to form the double-membrane vesicles necessary for TGEV replication, indicating that TMEM41B contributes to the formation of CoV replication organelles. Lastly, our data from a mouse infection model showed that the KO of this factor can strongly inhibit viral infection and delay the progression of a CoV disease. Our study revealed that targeting TMEM41B is a highly promising approach for the development of broad-spectrum anti-viral therapeutics.
. 2021 Dec 6;17(12):e1010113.
doi: 10.1371/journal.ppat.1010113. Online ahead of print.
Genome-scale CRISPR screen identifies TMEM41B as a multi-function host factor required for coronavirus replication
Limeng Sun[SUP] 1 2 [/SUP], Changzhi Zhao[SUP] 3 [/SUP], Zhen Fu[SUP] 1 2 [/SUP], Yanan Fu[SUP] 1 2 [/SUP], Zhelin Su[SUP] 1 2 [/SUP], Yangyang Li[SUP] 4 [/SUP], Yuan Zhou[SUP] 3 [/SUP], Yubei Tan[SUP] 1 2 [/SUP], Jingjin Li[SUP] 3 [/SUP], Yixin Xiang[SUP] 1 2 [/SUP], Xiongwei Nie[SUP] 3 [/SUP], Jinfu Zhang[SUP] 3 [/SUP], Fei Liu[SUP] 4 [/SUP], Shuhong Zhao[SUP] 3 5 [/SUP], Shengsong Xie[SUP] 3 [/SUP], Peng Guiqing[SUP] 1 2 [/SUP]
Affiliations
- PMID: 34871328
- DOI: 10.1371/journal.ppat.1010113
Abstract
Emerging coronaviruses (CoVs) pose a severe threat to human and animal health worldwide. To identify host factors required for CoV infection, we used α-CoV transmissible gastroenteritis virus (TGEV) as a model for genome-scale CRISPR knockout (KO) screening. Transmembrane protein 41B (TMEM41B) was found to be a bona fide host factor involved in infection by CoV and three additional virus families. We found that TMEM41B is critical for the internalization and early-stage replication of TGEV. Notably, our results also showed that cells lacking TMEM41B are unable to form the double-membrane vesicles necessary for TGEV replication, indicating that TMEM41B contributes to the formation of CoV replication organelles. Lastly, our data from a mouse infection model showed that the KO of this factor can strongly inhibit viral infection and delay the progression of a CoV disease. Our study revealed that targeting TMEM41B is a highly promising approach for the development of broad-spectrum anti-viral therapeutics.