Sci Adv . Apolipoprotein E mediates cell resistance to influenza virus infection

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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 ¹ , Miao Ji ^{1 2} , Xinyuan Liu ^{1 2} , Xiaotong Chen ¹ , Hongtao Liu ^{1 2} , Shihua Li ¹ , Baoqian Jia ¹ , Chao Li ^{1 2} , Lili Ren ³ , Xin Zhao ¹ , Qihui Wang ¹ , Yuhai Bi ¹ , Xu Tan ⁴ , Baidong Hou ⁵ , Xuyu Zhou ^{1 6} , Wenjie Tan ⁷ , Tao Deng ¹ , Jianwei Wang ³ , George Fu Gao ^{1 6 7} , Fuping Zhang ^{1 6}



Affiliations

• PMID: 36129973
• DOI: 10.1126/sciadv.abm6668

Free article

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^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.