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• W1865640430 abstract "Since its discovery in 1989, efforts to grow clinical isolates of the hepatitis C virus (HCV) in cell culture have met with limited success. Only the JFH-1 isolate has the capacity to replicate efficiently in cultured hepatoma cells without cell culture-adaptive mutations. We hypothesized that cultured cells lack one or more factors required for the replication of clinical isolates. To identify the missing factors, we transduced Huh-7.5 human hepatoma cells with a pooled lentivirus-based human complementary DNA (cDNA) library, transfected the cells with HCV subgenomic replicons lacking adaptive mutations, and selected for stable replicon colonies. This led to the identification of a single cDNA, SEC14L2, that enabled RNA replication of diverse HCV genotypes in several hepatoma cell lines. This effect was dose-dependent, and required the continuous presence of SEC14L2. Full-length HCV genomes also replicated and produced low levels of infectious virus. Remarkably, SEC14L2-expressing Huh-7.5 cells also supported HCV replication following inoculation with patient sera. Mechanistic studies suggest that SEC14L2 promotes HCV infection by enhancing vitamin E-mediated protection against lipid peroxidation. This provides a foundation for development of in vitro replication systems for all HCV isolates, creating a useful platform to dissect the mechanisms by which cell culture-adaptive mutations act." @default.
• W1865640430 created "2016-06-24" @default.
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• W1865640430 date "2015-08-01" @default.
• W1865640430 modified "2023-10-01" @default.
• W1865640430 title "SEC14L2 enables pan-genotype HCV replication in cell culture" @default.
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• W1865640430 doi "https://doi.org/10.1038/nature14899" @default.
• W1865640430 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4632207" @default.
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• W1865640430 hasPublicationYear "2015" @default.
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