tetano
Editor, Senior Moderator
Sci Adv
. 2022 Sep 23;8(38):eabm6668.
doi: 10.1126/sciadv.abm6668. Epub 2022 Sep 21.
Apolipoprotein E mediates cell resistance to influenza virus infection
Ping Gao[SUP] 1 [/SUP], Miao Ji[SUP] 1 2 [/SUP], Xinyuan Liu[SUP] 1 2 [/SUP], Xiaotong Chen[SUP] 1 [/SUP], Hongtao Liu[SUP] 1 2 [/SUP], Shihua Li[SUP] 1 [/SUP], Baoqian Jia[SUP] 1 [/SUP], Chao Li[SUP] 1 2 [/SUP], Lili Ren[SUP] 3 [/SUP], Xin Zhao[SUP] 1 [/SUP], Qihui Wang[SUP] 1 [/SUP], Yuhai Bi[SUP] 1 [/SUP], Xu Tan[SUP] 4 [/SUP], Baidong Hou[SUP] 5 [/SUP], Xuyu Zhou[SUP] 1 6 [/SUP], Wenjie Tan[SUP] 7 [/SUP], Tao Deng[SUP] 1 [/SUP], Jianwei Wang[SUP] 3 [/SUP], George Fu Gao[SUP] 1 6 7 [/SUP], Fuping Zhang[SUP] 1 6 [/SUP]
Affiliations
Abstract
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[SUP]hi[/SUP] 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.
. 2022 Sep 23;8(38):eabm6668.
doi: 10.1126/sciadv.abm6668. Epub 2022 Sep 21.
Apolipoprotein E mediates cell resistance to influenza virus infection
Ping Gao[SUP] 1 [/SUP], Miao Ji[SUP] 1 2 [/SUP], Xinyuan Liu[SUP] 1 2 [/SUP], Xiaotong Chen[SUP] 1 [/SUP], Hongtao Liu[SUP] 1 2 [/SUP], Shihua Li[SUP] 1 [/SUP], Baoqian Jia[SUP] 1 [/SUP], Chao Li[SUP] 1 2 [/SUP], Lili Ren[SUP] 3 [/SUP], Xin Zhao[SUP] 1 [/SUP], Qihui Wang[SUP] 1 [/SUP], Yuhai Bi[SUP] 1 [/SUP], Xu Tan[SUP] 4 [/SUP], Baidong Hou[SUP] 5 [/SUP], Xuyu Zhou[SUP] 1 6 [/SUP], Wenjie Tan[SUP] 7 [/SUP], Tao Deng[SUP] 1 [/SUP], Jianwei Wang[SUP] 3 [/SUP], George Fu Gao[SUP] 1 6 7 [/SUP], Fuping Zhang[SUP] 1 6 [/SUP]
Affiliations
- PMID: 36129973
- DOI: 10.1126/sciadv.abm6668
Abstract
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[SUP]hi[/SUP] 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.