Journal article
Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication
Cell reports (Cambridge), Vol.23(2), pp.596-607
04/10/2018
DOI: 10.1016/j.celrep.2018.03.045
PMCID: PMC5939577
PMID: 29642015
Abstract
The emergence of influenza A viruses (IAVs) from zoonotic reservoirs poses a great threat to human health. As seasonal vaccines are ineffective against zoonotic strains, and newly transmitted viruses can quickly acquire drug resistance, there remains a need for host-directed therapeutics against IAVs. Here, we performed a genome-scale CRISPR/Cas9 knockout screen in human lung epithelial cells with a human isolate of an avian H5N1 strain. Several genes involved in sialic acid biosynthesis and related glycosylation pathways were highly enriched post-H5N1 selection, including SLC35A1, a sialic acid transporter essential for IAV receptor expression and thus viral entry. Importantly, we have identified capicua (CIC) as a negative regulator of cell-intrinsic immunity, as loss of CIC resulted in heightened antiviral responses and restricted replication of multiple viruses. Therefore, our study demonstrates that the CRISPR/Cas9 system can be utilized for the discovery of host factors critical for the replication of intracellular pathogens.
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•Genome-wide CRISPR/Cas9 screen used to identify pro-viral IAV host factors•Host factors identified in viral entry and regulation of antiviral gene expression•Sialic acid transporter SLC35A1 is essential for viral receptor expression•Transcriptional repressor CIC is a negative regulator of cell-intrinsic immunity
Using a genome-wide CRISPR/Cas9 screen, Han et al. demonstrate that the major hit, the sialic acid transporter SLC35A1, is an essential host factor for IAV entry. In addition, they identify the DNA-binding transcriptional repressor CIC as a negative regulator of cell-intrinsic immunity.
Details
- Title: Subtitle
- Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication
- Creators
- Julianna Han - Department of Microbiology, The University of Chicago, Chicago, IL 60637, USAJasmine T Perez - Department of Microbiology, The University of Chicago, Chicago, IL 60637, USACindy Chen - Department of Microbiology, The University of Chicago, Chicago, IL 60637, USAYan Li - Center for Research Informatics, The University of Chicago, Chicago, IL 60637, USAAsiel Benitez - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAMatheswaran Kandasamy - Department of Microbiology, The University of Chicago, Chicago, IL 60637, USAYoontae Lee - Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Republic of KoreaJorge Andrade - Center for Research Informatics, The University of Chicago, Chicago, IL 60637, USABenjamin tenOever - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USABalaji Manicassamy - Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.23(2), pp.596-607
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.celrep.2018.03.045
- PMID
- 29642015
- PMCID
- PMC5939577
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases, award: R01AI123359, R01AI127775; DOI: 10.13039/100006108, name: National Center for Advancing Translational Sciences, award: UL1 TR000430; DOI: 10.13039/100007234, name: University of Chicago, award: R01AI123359-02S1, T32GM007183
- Language
- English
- Date published
- 04/10/2018
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083883802771
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