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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.
Han J1, Perez JT1, Chen C1, Li Y2, Benitez A3, Kandasamy M1, Lee Y4, Andrade J2, tenOever B3, Manicassamy B5.
Author information
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 DOI: 10.1016/j.celrep.2018.03.045
Genome-wide CRISPR/Cas9 Screen Identifies Host Factors Essential for Influenza Virus Replication.
Han J1, Perez JT1, Chen C1, Li Y2, Benitez A3, Kandasamy M1, Lee Y4, Andrade J2, tenOever B3, Manicassamy B5.
Author information
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 DOI: 10.1016/j.celrep.2018.03.045