Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection
Identifieur interne : 000147 ( Main/Exploration ); précédent : 000146; suivant : 000148Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection
Auteurs : Bo Li [États-Unis] ; Sara M. Clohisey ; Bing Shao Chia [États-Unis] ; Bo Wang ; Ang Cui [États-Unis] ; Thomas Eisenhaure [États-Unis] ; Lawrence D. Schweitzer [États-Unis] ; Paul Hoover [États-Unis] ; Nicholas J. Parkinson ; Aharon Nachshon [Israël] ; Nikki Smith ; Tim Regan ; David Farr ; Michael U. Gutmann ; Syed Irfan Bukhari [États-Unis] ; Andrew Law ; Maya Sangesland [États-Unis] ; Irit Gat-Viks [États-Unis, Israël] ; Paul Digard ; Shobha Vasudevan [États-Unis] ; Daniel Lingwood [États-Unis] ; David H. Dockrell [Royaume-Uni] ; John G. Doench [États-Unis] ; J. Kenneth Baillie ; Nir Hacohen [États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2020.
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,
Url:
DOI: 10.1038/s41467-019-13965-x
PubMed: 31919360
PubMed Central: 6952391
Affiliations:
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Kenneth Baillie</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution>Roslin Institute,</institution><institution>University of Edinburgh,</institution></institution-wrap>Easter Bush, EH25 9RG UK</nlm:aff><wicri:noCountry code="subfield">EH25 9RG UK</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff10"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0709 1919</institution-id><institution-id institution-id-type="GRID">grid.418716.d</institution-id><institution>Intensive Care Unit, Royal Infirmary Edinburgh,</institution></institution-wrap>Edinburgh, EH16 5SA UK</nlm:aff><wicri:noCountry code="subfield">EH16 5SA UK</wicri:noCountry></affiliation></author><author><name sortKey="Hacohen, Nir" sort="Hacohen, Nir" uniqKey="Hacohen N" first="Nir" last="Hacohen">Nir Hacohen</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.66859.34</institution-id><institution>Broad Institute of MIT and Harvard,</institution></institution-wrap>415 Main Street, Cambridge, MA 02142 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>415 Main Street, Cambridge</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff11"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0386 9924</institution-id><institution-id institution-id-type="GRID">grid.32224.35</institution-id><institution>Massachusetts General Hospital Cancer Center,</institution></institution-wrap>Boston, MA 02129 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31919360</idno><idno type="pmc">6952391</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952391</idno><idno type="RBID">PMC:6952391</idno><idno type="doi">10.1038/s41467-019-13965-x</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000153</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000153</idno><idno type="wicri:Area/Pmc/Curation">000153</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000153</idno><idno type="wicri:Area/Pmc/Checkpoint">000137</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000137</idno><idno type="wicri:Area/Ncbi/Merge">000E17</idno><idno type="wicri:Area/Ncbi/Curation">000E17</idno><idno type="wicri:Area/Ncbi/Checkpoint">000E17</idno><idno type="wicri:Area/Main/Merge">000147</idno><idno type="wicri:Area/Main/Curation">000147</idno><idno type="wicri:Area/Main/Exploration">000147</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection</title><author><name sortKey="Li, Bo" sort="Li, Bo" uniqKey="Li B" first="Bo" last="Li">Bo Li</name><affiliation><nlm:aff id="Aff1">Harvard University Virology Program, Harvfvard Medical School, Boston, MA02142 USA</nlm:aff><wicri:noCountry code="subfield">MA02142 USA</wicri:noCountry></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.66859.34</institution-id><institution>Broad Institute of MIT and Harvard,</institution></institution-wrap>415 Main Street, Cambridge, MA 02142 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>415 Main Street, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Clohisey, Sara M" sort="Clohisey, Sara M" uniqKey="Clohisey S" first="Sara M." last="Clohisey">Sara M. Clohisey</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution>Roslin Institute,</institution><institution>University of Edinburgh,</institution></institution-wrap>Easter Bush, EH25 9RG UK</nlm:aff><wicri:noCountry code="subfield">EH25 9RG UK</wicri:noCountry></affiliation></author><author><name sortKey="Chia, Bing Shao" sort="Chia, Bing Shao" uniqKey="Chia B" first="Bing Shao" last="Chia">Bing Shao Chia</name><affiliation><nlm:aff id="Aff1">Harvard University Virology Program, Harvfvard Medical School, Boston, MA02142 USA</nlm:aff><wicri:noCountry code="subfield">MA02142 USA</wicri:noCountry></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.66859.34</institution-id><institution>Broad Institute of MIT and Harvard,</institution></institution-wrap>415 Main Street, Cambridge, MA 02142 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>415 Main Street, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Wang, Bo" sort="Wang, Bo" uniqKey="Wang B" first="Bo" last="Wang">Bo Wang</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution>Roslin Institute,</institution><institution>University of Edinburgh,</institution></institution-wrap>Easter Bush, EH25 9RG UK</nlm:aff><wicri:noCountry code="subfield">EH25 9RG UK</wicri:noCountry></affiliation></author><author><name sortKey="Cui, Ang" sort="Cui, Ang" uniqKey="Cui A" first="Ang" last="Cui">Ang Cui</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.66859.34</institution-id><institution>Broad Institute of MIT and Harvard,</institution></institution-wrap>415 Main Street, Cambridge, MA 02142 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>415 Main Street, Cambridge</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">000000041936754X</institution-id><institution-id institution-id-type="GRID">grid.38142.3c</institution-id><institution>Harvard-MIT Health Sciences and Technology,</institution><institution>Harvard Medical School,</institution></institution-wrap>Boston, MA 02115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation></author><author><name sortKey="Eisenhaure, Thomas" sort="Eisenhaure, Thomas" uniqKey="Eisenhaure T" first="Thomas" last="Eisenhaure">Thomas Eisenhaure</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.66859.34</institution-id><institution>Broad Institute of MIT and Harvard,</institution></institution-wrap>415 Main Street, Cambridge, MA 02142 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>415 Main Street, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Schweitzer, Lawrence D" sort="Schweitzer, Lawrence D" uniqKey="Schweitzer L" first="Lawrence D." last="Schweitzer">Lawrence D. Schweitzer</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.66859.34</institution-id><institution>Broad Institute of MIT and Harvard,</institution></institution-wrap>415 Main Street, Cambridge, MA 02142 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>415 Main Street, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Hoover, Paul" sort="Hoover, Paul" uniqKey="Hoover P" first="Paul" last="Hoover">Paul Hoover</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.66859.34</institution-id><institution>Broad Institute of MIT and Harvard,</institution></institution-wrap>415 Main Street, Cambridge, MA 02142 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>415 Main Street, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Parkinson, Nicholas J" sort="Parkinson, Nicholas J" uniqKey="Parkinson N" first="Nicholas J." last="Parkinson">Nicholas J. Parkinson</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution>Roslin Institute,</institution><institution>University of Edinburgh,</institution></institution-wrap>Easter Bush, EH25 9RG UK</nlm:aff><wicri:noCountry code="subfield">EH25 9RG UK</wicri:noCountry></affiliation></author><author><name sortKey="Nachshon, Aharon" sort="Nachshon, Aharon" uniqKey="Nachshon A" first="Aharon" last="Nachshon">Aharon Nachshon</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1937 0546</institution-id><institution-id institution-id-type="GRID">grid.12136.37</institution-id><institution>School of Molecular Cell Biology and Biotechnology, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences,</institution><institution>Tel Aviv University,</institution></institution-wrap>Tel Aviv, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Tel Aviv</wicri:regionArea></affiliation></author><author><name sortKey="Smith, Nikki" sort="Smith, Nikki" uniqKey="Smith N" first="Nikki" last="Smith">Nikki Smith</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution>Roslin Institute,</institution><institution>University of Edinburgh,</institution></institution-wrap>Easter Bush, EH25 9RG UK</nlm:aff><wicri:noCountry code="subfield">EH25 9RG UK</wicri:noCountry></affiliation></author><author><name sortKey="Regan, Tim" sort="Regan, Tim" uniqKey="Regan T" first="Tim" last="Regan">Tim Regan</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution>Roslin Institute,</institution><institution>University of Edinburgh,</institution></institution-wrap>Easter Bush, EH25 9RG UK</nlm:aff><wicri:noCountry code="subfield">EH25 9RG UK</wicri:noCountry></affiliation></author><author><name sortKey="Farr, David" sort="Farr, David" uniqKey="Farr D" first="David" last="Farr">David Farr</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution>Roslin Institute,</institution><institution>University of Edinburgh,</institution></institution-wrap>Easter Bush, EH25 9RG UK</nlm:aff><wicri:noCountry code="subfield">EH25 9RG UK</wicri:noCountry></affiliation></author><author><name sortKey="Gutmann, Michael U" sort="Gutmann, Michael U" uniqKey="Gutmann M" first="Michael U." last="Gutmann">Michael U. Gutmann</name><affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution>School of informatics,</institution><institution>University of Edinburgh,</institution></institution-wrap>Edinburgh, EH8 9YL UK</nlm:aff><wicri:noCountry code="subfield">EH8 9YL UK</wicri:noCountry></affiliation></author><author><name sortKey="Bukhari, Syed Irfan" sort="Bukhari, Syed Irfan" uniqKey="Bukhari S" first="Syed Irfan" last="Bukhari">Syed Irfan Bukhari</name><affiliation wicri:level="2"><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">000000041936754X</institution-id><institution-id institution-id-type="GRID">grid.38142.3c</institution-id><institution>Center for Cancer Research, Massachusetts General hospital,</institution><institution>Harvard Medical School,</institution></institution-wrap>Boston, MA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation></author><author><name sortKey="Law, Andrew" sort="Law, Andrew" uniqKey="Law A" first="Andrew" last="Law">Andrew Law</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution>Roslin Institute,</institution><institution>University of Edinburgh,</institution></institution-wrap>Easter Bush, EH25 9RG UK</nlm:aff><wicri:noCountry code="subfield">EH25 9RG UK</wicri:noCountry></affiliation></author><author><name sortKey="Sangesland, Maya" sort="Sangesland, Maya" uniqKey="Sangesland M" first="Maya" last="Sangesland">Maya Sangesland</name><affiliation wicri:level="2"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="ISNI">000000041936754X</institution-id><institution-id institution-id-type="GRID">grid.38142.3c</institution-id><institution>The Ragon Institute of Massachusetts General Hospital,</institution><institution>MIT and Harvard University,</institution></institution-wrap>Cambridge, MA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Gat Viks, Irit" sort="Gat Viks, Irit" uniqKey="Gat Viks I" first="Irit" last="Gat-Viks">Irit Gat-Viks</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.66859.34</institution-id><institution>Broad Institute of MIT and Harvard,</institution></institution-wrap>415 Main Street, Cambridge, MA 02142 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>415 Main Street, Cambridge</wicri:cityArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1937 0546</institution-id><institution-id institution-id-type="GRID">grid.12136.37</institution-id><institution>School of Molecular Cell Biology and Biotechnology, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences,</institution><institution>Tel Aviv University,</institution></institution-wrap>Tel Aviv, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Tel Aviv</wicri:regionArea></affiliation></author><author><name sortKey="Digard, Paul" sort="Digard, Paul" uniqKey="Digard P" first="Paul" last="Digard">Paul Digard</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution>Roslin Institute,</institution><institution>University of Edinburgh,</institution></institution-wrap>Easter Bush, EH25 9RG UK</nlm:aff><wicri:noCountry code="subfield">EH25 9RG UK</wicri:noCountry></affiliation></author><author><name sortKey="Vasudevan, Shobha" sort="Vasudevan, Shobha" uniqKey="Vasudevan S" first="Shobha" last="Vasudevan">Shobha Vasudevan</name><affiliation wicri:level="2"><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">000000041936754X</institution-id><institution-id institution-id-type="GRID">grid.38142.3c</institution-id><institution>Center for Cancer Research, Massachusetts General hospital,</institution><institution>Harvard Medical School,</institution></institution-wrap>Boston, MA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation></author><author><name sortKey="Lingwood, Daniel" sort="Lingwood, Daniel" uniqKey="Lingwood D" first="Daniel" last="Lingwood">Daniel Lingwood</name><affiliation wicri:level="2"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="ISNI">000000041936754X</institution-id><institution-id institution-id-type="GRID">grid.38142.3c</institution-id><institution>The Ragon Institute of Massachusetts General Hospital,</institution><institution>MIT and Harvard University,</institution></institution-wrap>Cambridge, MA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Dockrell, David H" sort="Dockrell, David H" uniqKey="Dockrell D" first="David H." last="Dockrell">David H. Dockrell</name><affiliation wicri:level="1"><nlm:aff id="Aff9"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution>MRC Center for Inflammation Research,</institution><institution>University of Edinburgh,</institution></institution-wrap>Edinburgh, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Edinburgh</wicri:regionArea></affiliation></author><author><name sortKey="Doench, John G" sort="Doench, John G" uniqKey="Doench J" first="John G." last="Doench">John G. Doench</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.66859.34</institution-id><institution>Broad Institute of MIT and Harvard,</institution></institution-wrap>415 Main Street, Cambridge, MA 02142 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>415 Main Street, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Baillie, J Kenneth" sort="Baillie, J Kenneth" uniqKey="Baillie J" first="J. Kenneth" last="Baillie">J. Kenneth Baillie</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7988</institution-id><institution-id institution-id-type="GRID">grid.4305.2</institution-id><institution>Roslin Institute,</institution><institution>University of Edinburgh,</institution></institution-wrap>Easter Bush, EH25 9RG UK</nlm:aff><wicri:noCountry code="subfield">EH25 9RG UK</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff10"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0709 1919</institution-id><institution-id institution-id-type="GRID">grid.418716.d</institution-id><institution>Intensive Care Unit, Royal Infirmary Edinburgh,</institution></institution-wrap>Edinburgh, EH16 5SA UK</nlm:aff><wicri:noCountry code="subfield">EH16 5SA UK</wicri:noCountry></affiliation></author><author><name sortKey="Hacohen, Nir" sort="Hacohen, Nir" uniqKey="Hacohen N" first="Nir" last="Hacohen">Nir Hacohen</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.66859.34</institution-id><institution>Broad Institute of MIT and Harvard,</institution></institution-wrap>415 Main Street, Cambridge, MA 02142 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>415 Main Street, Cambridge</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="Aff11"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0386 9924</institution-id><institution-id institution-id-type="GRID">grid.32224.35</institution-id><institution>Massachusetts General Hospital Cancer Center,</institution></institution-wrap>Boston, MA 02129 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Boston</wicri:cityArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">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, <italic>WDR7, CCDC115</italic> and <italic>TMEM199</italic>, demonstrating that these genes are essential for viral entry and regulation of V-type ATPase assembly. We also find that <italic>CMTR1</italic>, 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Shrestha, S S" uniqKey="Shrestha S">S. S. Shrestha</name></author><author><name sortKey="Swerdlow, D L" uniqKey="Swerdlow D">D. L. Swerdlow</name></author><author><name sortKey="Borse, R H" uniqKey="Borse R">R. H. Borse</name></author><author><name sortKey="Prabhu, V S" uniqKey="Prabhu V">V. S. Prabhu</name></author><author><name sortKey="Finelli, L" uniqKey="Finelli L">L. Finelli</name></author><author><name sortKey="Atkins, C Y" uniqKey="Atkins C">C. Y. Atkins</name></author><author><name sortKey="Owusu Edusei, K" uniqKey="Owusu Edusei K">K. Owusu-Edusei</name></author><author><name sortKey="Bell, B" uniqKey="Bell B">B. Bell</name></author><author><name sortKey="Mead, P S" uniqKey="Mead P">P. S. Mead</name></author><author><name sortKey="Biggerstaff, M" uniqKey="Biggerstaff M">M. Biggerstaff</name></author><author><name sortKey="Brammer, L" uniqKey="Brammer L">L. Brammer</name></author><author><name sortKey="Davidson, H" uniqKey="Davidson H">H. Davidson</name></author><author><name sortKey="Jernigan, D" uniqKey="Jernigan D">D. Jernigan</name></author><author><name sortKey="Jhung, M A" uniqKey="Jhung M">M. A. Jhung</name></author><author><name sortKey="Kamimoto, L A" uniqKey="Kamimoto L">L. A. Kamimoto</name></author><author><name sortKey="Merlin, T L" uniqKey="Merlin T">T. L. Merlin</name></author><author><name sortKey="Nowell, M" uniqKey="Nowell M">M. Nowell</name></author><author><name sortKey="Redd, S C" uniqKey="Redd S">S. C. Redd</name></author><author><name sortKey="Reed, C" uniqKey="Reed C">C. Reed</name></author><author><name sortKey="Schuchat, A" uniqKey="Schuchat A">A. Schuchat</name></author><author><name sortKey="Meltzer, M I" uniqKey="Meltzer M">M. I. Meltzer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simonsen, Lone" uniqKey="Simonsen L">Lone Simonsen</name></author><author><name sortKey="Spreeuwenberg, Peter" uniqKey="Spreeuwenberg P">Peter Spreeuwenberg</name></author><author><name sortKey="Lustig, Roger" uniqKey="Lustig R">Roger Lustig</name></author><author><name sortKey="Taylor, Robert J" uniqKey="Taylor R">Robert J. Taylor</name></author><author><name sortKey="Fleming, Douglas M" uniqKey="Fleming D">Douglas M. Fleming</name></author><author><name sortKey="Kroneman, Madelon" uniqKey="Kroneman M">Madelon Kroneman</name></author><author><name sortKey="Van Kerkhove, Maria D" uniqKey="Van Kerkhove M">Maria D. Van Kerkhove</name></author><author><name sortKey="Mounts, Anthony W" uniqKey="Mounts A">Anthony W. Mounts</name></author><author><name sortKey="Paget, W John" uniqKey="Paget W">W. 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Russell</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Maydeu Olivares, Albert" uniqKey="Maydeu Olivares A">Albert Maydeu-Olivares</name></author></analytic></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Israël</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Massachusetts</li></region></list><tree><noCountry><name sortKey="Baillie, J Kenneth" sort="Baillie, J Kenneth" uniqKey="Baillie J" first="J. Kenneth" last="Baillie">J. Kenneth Baillie</name><name sortKey="Clohisey, Sara M" sort="Clohisey, Sara M" uniqKey="Clohisey S" first="Sara M." last="Clohisey">Sara M. Clohisey</name><name sortKey="Digard, Paul" sort="Digard, Paul" uniqKey="Digard P" first="Paul" last="Digard">Paul Digard</name><name sortKey="Farr, David" sort="Farr, David" uniqKey="Farr D" first="David" last="Farr">David Farr</name><name sortKey="Gutmann, Michael U" sort="Gutmann, Michael U" uniqKey="Gutmann M" first="Michael U." last="Gutmann">Michael U. Gutmann</name><name sortKey="Law, Andrew" sort="Law, Andrew" uniqKey="Law A" first="Andrew" last="Law">Andrew Law</name><name sortKey="Parkinson, Nicholas J" sort="Parkinson, Nicholas J" uniqKey="Parkinson N" first="Nicholas J." last="Parkinson">Nicholas J. Parkinson</name><name sortKey="Regan, Tim" sort="Regan, Tim" uniqKey="Regan T" first="Tim" last="Regan">Tim Regan</name><name sortKey="Smith, Nikki" sort="Smith, Nikki" uniqKey="Smith N" first="Nikki" last="Smith">Nikki Smith</name><name sortKey="Wang, Bo" sort="Wang, Bo" uniqKey="Wang B" first="Bo" last="Wang">Bo Wang</name></noCountry><country name="États-Unis"><region name="Massachusetts"><name sortKey="Li, Bo" sort="Li, Bo" uniqKey="Li B" first="Bo" last="Li">Bo Li</name></region><name sortKey="Bukhari, Syed Irfan" sort="Bukhari, Syed Irfan" uniqKey="Bukhari S" first="Syed Irfan" last="Bukhari">Syed Irfan Bukhari</name><name sortKey="Chia, Bing Shao" sort="Chia, Bing Shao" uniqKey="Chia B" first="Bing Shao" last="Chia">Bing Shao Chia</name><name sortKey="Cui, Ang" sort="Cui, Ang" uniqKey="Cui A" first="Ang" last="Cui">Ang Cui</name><name sortKey="Cui, Ang" sort="Cui, Ang" uniqKey="Cui A" first="Ang" last="Cui">Ang Cui</name><name sortKey="Doench, John G" sort="Doench, John G" uniqKey="Doench J" first="John G." last="Doench">John G. Doench</name><name sortKey="Eisenhaure, Thomas" sort="Eisenhaure, Thomas" uniqKey="Eisenhaure T" first="Thomas" last="Eisenhaure">Thomas Eisenhaure</name><name sortKey="Gat Viks, Irit" sort="Gat Viks, Irit" uniqKey="Gat Viks I" first="Irit" last="Gat-Viks">Irit Gat-Viks</name><name sortKey="Hacohen, Nir" sort="Hacohen, Nir" uniqKey="Hacohen N" first="Nir" last="Hacohen">Nir Hacohen</name><name sortKey="Hacohen, Nir" sort="Hacohen, Nir" uniqKey="Hacohen N" first="Nir" last="Hacohen">Nir Hacohen</name><name sortKey="Hoover, Paul" sort="Hoover, Paul" uniqKey="Hoover P" first="Paul" last="Hoover">Paul Hoover</name><name sortKey="Lingwood, Daniel" sort="Lingwood, Daniel" uniqKey="Lingwood D" first="Daniel" last="Lingwood">Daniel Lingwood</name><name sortKey="Sangesland, Maya" sort="Sangesland, Maya" uniqKey="Sangesland M" first="Maya" last="Sangesland">Maya Sangesland</name><name sortKey="Schweitzer, Lawrence D" sort="Schweitzer, Lawrence D" uniqKey="Schweitzer L" first="Lawrence D." last="Schweitzer">Lawrence D. Schweitzer</name><name sortKey="Vasudevan, Shobha" sort="Vasudevan, Shobha" uniqKey="Vasudevan S" first="Shobha" last="Vasudevan">Shobha Vasudevan</name></country><country name="Israël"><noRegion><name sortKey="Nachshon, Aharon" sort="Nachshon, Aharon" uniqKey="Nachshon A" first="Aharon" last="Nachshon">Aharon Nachshon</name></noRegion><name sortKey="Gat Viks, Irit" sort="Gat Viks, Irit" uniqKey="Gat Viks I" first="Irit" last="Gat-Viks">Irit Gat-Viks</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Dockrell, David H" sort="Dockrell, David H" uniqKey="Dockrell D" first="David H." last="Dockrell">David H. Dockrell</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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