Genome-scale CRISPR screen identifies TMEM41B as a multi-function host factor required for coronavirus replication

• DOI: 10.1371/journal.ppat.1010113
• Publication Date: 2021-12-06T18:28:51Z
• Authors: Limeng Sun; Changzhi Zhao; Zhen Fu; Yanan Fu; Zhelin Su; Yangyang Li; Yuan Zhou; Yubei Tan; Jingjin Li; Yixin Xiang; Xiongwei Nie; Jinfu Zhang; Fei Liu; Shuhong Zhao; Shengsong Xie; Guiqing Peng
• Keywords: QH301-705.5; Swine; Infectious disease (medical specialty); Coronavirus Disease 2019 Research; FOS: Health sciences; Virus Replication; Gene; Mice; Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated proteins; 03 medical and health sciences; Biochemistry, Genetics and Molecular Biology; Virology; Health Sciences; Viral replication; Genetics; Pathology; Animals; Disease; CRISPR Systems; Biology (General); Aetiology, Diagnosis, and Management of Myocarditis; Molecular Biology; Biology; Organelles; 0303 health sciences; Genome; Gastroenteritis, Transmissible, of Swine; Transmissible gastroenteritis virus; Membrane Proteins; Life Sciences; RC581-607; Virus; 3. Good health; Mice, Inbred C57BL; Coronavirus; Coronavirus disease 2019 (COVID-19); Infectious Diseases; CRISPR; FOS: Biological sciences; Host-Pathogen Interactions; Medicine; Immunologic diseases. Allergy; CRISPR-Cas Systems; Cardiology and Cardiovascular Medicine; Host factor; Research Article

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.