Apolipoprotein E mediates cell resistance to influenza virus infection.

Autor: Gao P; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China., Ji M; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Liu X; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Chen X; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China., Liu H; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Li S; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China., Jia B; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China., Li C; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Ren L; MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China., Zhao X; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China., Wang Q; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China., Bi Y; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China., Tan X; School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China., Hou B; Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., Zhou X; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China., Tan W; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China., Deng T; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China., Wang J; MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China., Gao GF; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China., Zhang F; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2022 Sep 23; Vol. 8 (38), pp. eabm6668. Date of Electronic Publication: 2022 Sep 21.
DOI: 10.1126/sciadv.abm6668
Abstrakt: Viruses exploit host cell machinery to support their replication. Defining the cellular proteins and processes required for a virus during infection is crucial to understanding the mechanisms of virally induced disease and designing host-directed therapeutics. Here, we perform a genome-wide CRISPR-Cas9-based screening in lung epithelial cells infected with the PR/8/NS1-GFP virus and use GFP hi cell as a unique screening marker to identify host factors that inhibit influenza A virus (IAV) infection. We discovered that APOE affects influenza virus infection both in vitro and in vivo. Cell deficiency in APOE conferred substantially increased susceptibility to IAV; mice deficient in APOE manifested more severe lung pathology, increased virus load, and decreased survival rate. Mechanistically, lack of cell-produced APOE results in impaired cell cholesterol homeostasis, enhancing influenza virus attachment. Thus, we identified a previously unrecognized role of APOE in restraining IAV infection.
Databáze: MEDLINE