Lipidomics identifies a requirement for peroxisomal function during influenza virus replication.
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ABSTRACT:
SUBMITTER: Tanner LB
PROVIDER: S-EPMC4076098 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The emergence of influenza A viruses (IAV) 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 IAV. 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.
2018-02-28 | GSE111166 | GEO
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