Genome-scale CRISPR screen identifies TMEM41B as a multi-function host factor required for coronavirus replication.
PLoS Pathog
; 17(12): e1010113, 2021 12.
Article
in English
| MEDLINE | ID: covidwho-1553552
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Replication
/
Organelles
/
Transmissible gastroenteritis virus
/
Host-Pathogen Interactions
/
CRISPR-Cas Systems
/
Gastroenteritis, Transmissible, of Swine
/
Membrane Proteins
Limits:
Animals
Language:
English
Journal:
PLoS Pathog
Year:
2021
Document Type:
Article
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