SEC14L2 enables pan-genotype HCV replication in cell culture

摘要: Since its discovery in 1989, efforts to grow clinical isolates of the hepatitis C virus (HCV) cell culture have met with limited success. Only JFH-1 isolate has capacity replicate efficiently cultured hepatoma cells without culture-adaptive mutations. We hypothesized that lack one or more factors required for replication isolates. To identify missing factors, we transduced Huh-7.5 human a pooled lentivirus-based complementary DNA (cDNA) library, transfected HCV subgenomic replicons lacking adaptive mutations, and selected stable replicon colonies. This led identification single cDNA, SEC14L2, enabled RNA diverse genotypes several lines. effect was dose-dependent, continuous presence SEC14L2. Full-length genomes also replicated produced low levels infectious virus. Remarkably, SEC14L2-expressing supported following inoculation patient sera. Mechanistic studies suggest SEC14L2 promotes infection by enhancing vitamin E-mediated protection against lipid peroxidation. provides foundation development vitro systems all isolates, creating useful platform dissect mechanisms which mutations act.