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

Author

Listed:
  • Bo Li

    (Harvard University Virology Program, Harvfvard Medical School
    Broad Institute of MIT and Harvard)

  • Sara M. Clohisey

    (University of Edinburgh)

  • Bing Shao Chia

    (Harvard University Virology Program, Harvfvard Medical School
    Broad Institute of MIT and Harvard)

  • Bo Wang

    (University of Edinburgh)

  • Ang Cui

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Thomas Eisenhaure

    (Broad Institute of MIT and Harvard)

  • Lawrence D. Schweitzer

    (Broad Institute of MIT and Harvard)

  • Paul Hoover

    (Broad Institute of MIT and Harvard)

  • Nicholas J. Parkinson

    (University of Edinburgh)

  • Aharon Nachshon

    (Tel Aviv University)

  • Nikki Smith

    (University of Edinburgh)

  • Tim Regan

    (University of Edinburgh)

  • David Farr

    (University of Edinburgh)

  • Michael U. Gutmann

    (University of Edinburgh)

  • Syed Irfan Bukhari

    (Harvard Medical School)

  • Andrew Law

    (University of Edinburgh)

  • Maya Sangesland

    (MIT and Harvard University)

  • Irit Gat-Viks

    (Broad Institute of MIT and Harvard
    Tel Aviv University)

  • Paul Digard

    (University of Edinburgh)

  • Shobha Vasudevan

    (Harvard Medical School)

  • Daniel Lingwood

    (MIT and Harvard University)

  • David H. Dockrell

    (University of Edinburgh)

  • John G. Doench

    (Broad Institute of MIT and Harvard)

  • J. Kenneth Baillie

    (University of Edinburgh
    Intensive Care Unit, Royal Infirmary Edinburgh)

  • Nir Hacohen

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital Cancer Center)

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.

Suggested Citation

  • Bo Li & Sara M. Clohisey & Bing Shao Chia & Bo Wang & Ang Cui & Thomas Eisenhaure & Lawrence D. Schweitzer & Paul Hoover & Nicholas J. Parkinson & Aharon Nachshon & Nikki Smith & Tim Regan & David Far, 2020. "Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13965-x
    DOI: 10.1038/s41467-019-13965-x
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    Cited by:

    1. Yutian Zou & Shaoquan Zheng & Xinhua Xie & Feng Ye & Xiaoqian Hu & Zhi Tian & Shu-Mei Yan & Lu Yang & Yanan Kong & Yuhui Tang & Wenwen Tian & Jindong Xie & Xinpei Deng & Yan Zeng & Zhe-Sheng Chen & Ha, 2022. "N6-methyladenosine regulated FGFR4 attenuates ferroptotic cell death in recalcitrant HER2-positive breast cancer," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Joseph D. Trimarco & Sarah L. Nelson & Ryan R. Chaparian & Alexandra I. Wells & Nathan B. Murray & Parastoo Azadi & Carolyn B. Coyne & Nicholas S. Heaton, 2022. "Cellular glycan modification by B3GAT1 broadly restricts influenza virus infection," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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