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Nat. Comm. Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection

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  • Nat. Comm. Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection


    Nat Commun. 2020 Jan 9;11(1):164. doi: 10.1038/s41467-019-13965-x. Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection.

    Li B1,2, Clohisey SM3, Chia BS1,2, Wang B3, Cui A2,4, Eisenhaure T2, Schweitzer LD2, Hoover P2, Parkinson NJ3, Nachshon A5, Smith N3, Regan T3, Farr D3, Gutmann MU6, Bukhari SI7, Law A3, Sangesland M8, Gat-Viks I2,5, Digard P3, Vasudevan S7, Lingwood D8, Dockrell DH9, Doench JG2, Baillie JK10,11, Hacohen N12,13.
    Author information

    Abstract

    Host dependency factors that are required for influenza A virus infection may serve as therapeutic targets as the virus is less likely to bypass them under drug-mediated selection pressure. Previous attempts to identify host factors have produced largely divergent results, with few overlapping hits across different studies. Here, we perform a genome-wide CRISPR/Cas9 screen and devise a new approach, meta-analysis by information content (MAIC) to systematically combine our results with prior evidence for influenza host factors. MAIC out-performs other meta-analysis methods when using our CRISPR screen as validation data. We validate the host factors, WDR7, CCDC115 and TMEM199, demonstrating that these genes are essential for viral entry and regulation of V-type ATPase assembly. We also find that CMTR1, a human mRNA cap methyltransferase, is required for efficient viral cap snatching and regulation of a cell autonomous immune response, and provides synergistic protection with the influenza endonuclease inhibitor Xofluza.


    PMID: 31919360 PMCID: PMC6952391 DOI: 10.1038/s41467-019-13965-x
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