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Cell Rep. 2018 Apr 10;23(2):596-607. doi: 10.1016/j.celrep.2018.03.045.

Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication.

Author information

1
Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA.
2
Center for Research Informatics, The University of Chicago, Chicago, IL 60637, USA.
3
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
4
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Republic of Korea.
5
Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: bmanicassamy@bsd.uchicago.edu.

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.

KEYWORDS:

CIC; CRISPR/Cas9 screen; Capicua; GeCKO; H5N1; SLC35A1; cell-intrinsic immunity; host factors; influenza virus; sialic acid pathway

PMID:
29642015
PMCID:
PMC5939577
DOI:
10.1016/j.celrep.2018.03.045
[Indexed for MEDLINE]
Free PMC Article

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