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

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 Farr; Michael U. Gutmann; Syed Irfan Bukhari; Andrew Law; Maya Sangesland; Irit Gat-Viks; Paul Digard; Shobha Vasudevan; Daniel Lingwood; David H. Dockrell; John G. Doench; J. Kenneth Baillie; Nir Hacohen

doi:10.1038/s41467-019-13965-x

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

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 Farr, Michael U. Gutmann, Syed Irfan Bukhari, Andrew Law, Maya Sangesland, Irit Gat-Viks, Paul Digard, Shobha VasudevanDaniel Lingwood, David H. Dockrell, John G. Doench, J. Kenneth Baillie, Nir Hacohen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

121 Scopus citations

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.

Original language	English
Article number	164
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13965-x
State	Published - 1 Dec 2020

Funding

Funders	Funder number
National Institutes of Health
National Human Genome Research Institute	P50HG006193
National Human Genome Research Institute
Wellcome Trust Centre for Mitochondrial Research	103258/Z/13/Z
Wellcome Trust Centre for Mitochondrial Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-019-13965-x

Cite this

Li, B., Clohisey, S. M., Chia, B. S., Wang, B., Cui, A., Eisenhaure, T., Schweitzer, L. D., Hoover, P., Parkinson, N. J., Nachshon, A., Smith, N., Regan, T., Farr, D., Gutmann, M. U., Bukhari, S. I., Law, A., Sangesland, M., Gat-Viks, I., Digard, P., ... Hacohen, N. (2020). Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection. Nature Communications, 11(1), Article 164. https://doi.org/10.1038/s41467-019-13965-x

@article{56ae2dcc0784434a9b4562df20fc7400,

title = "Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection",

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.",

author = "Bo Li and Clohisey, {Sara M.} and Chia, {Bing Shao} and Bo Wang and Ang Cui and Thomas Eisenhaure and Schweitzer, {Lawrence D.} and Paul Hoover and Parkinson, {Nicholas J.} and Aharon Nachshon and Nikki Smith and Tim Regan and David Farr and Gutmann, {Michael U.} and Bukhari, {Syed Irfan} and Andrew Law and Maya Sangesland and Irit Gat-Viks and Paul Digard and Shobha Vasudevan and Daniel Lingwood and Dockrell, {David H.} and Doench, {John G.} and Baillie, {J. Kenneth} and Nir Hacohen",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-019-13965-x",

language = "אנגלית",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Li, B, Clohisey, SM, Chia, BS, Wang, B, Cui, A, Eisenhaure, T, Schweitzer, LD, Hoover, P, Parkinson, NJ, Nachshon, A, Smith, N, Regan, T, Farr, D, Gutmann, MU, Bukhari, SI, Law, A, Sangesland, M, Gat-Viks, I, Digard, P, Vasudevan, S, Lingwood, D, Dockrell, DH, Doench, JG, Baillie, JK & Hacohen, N 2020, 'Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection', Nature Communications, vol. 11, no. 1, 164. https://doi.org/10.1038/s41467-019-13965-x

TY - JOUR

T1 - Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection

AU - Li, Bo

AU - Clohisey, Sara M.

AU - Chia, Bing Shao

AU - Wang, Bo

AU - Cui, Ang

AU - Eisenhaure, Thomas

AU - Schweitzer, Lawrence D.

AU - Hoover, Paul

AU - Parkinson, Nicholas J.

AU - Nachshon, Aharon

AU - Smith, Nikki

AU - Regan, Tim

AU - Farr, David

AU - Gutmann, Michael U.

AU - Bukhari, Syed Irfan

AU - Law, Andrew

AU - Sangesland, Maya

AU - Gat-Viks, Irit

AU - Digard, Paul

AU - Vasudevan, Shobha

AU - Lingwood, Daniel

AU - Dockrell, David H.

AU - Doench, John G.

AU - Baillie, J. Kenneth

AU - Hacohen, Nir

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85077696659&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-13965-x

DO - 10.1038/s41467-019-13965-x

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 31919360

AN - SCOPUS:85077696659

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 164

ER -

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

Abstract

Funding

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this