SEC14L2 is not a reliable predictor of HCV replication fitness

The replication of natural patient derived HCV strains in cell culture had been an elusive target until recently Saeed et al reported on a model where the expression of the protein SEC14L2 mediated protection against lipid peroxidation enabling the replication of patient derived virus in cell culture. We employed this model to investigate the role of SEC14L2 variability in the HCV life cycle in in vitro conditions. For this purpose we generated 13 different Huh-7.5 human hepatoma cell lines, each harbouring the one of the 13 most prevalent SEC14L2 SNPs described in the literature. We infected these cell lines with patient derived serum and quantified the HCV load after infection using qRT-PCR. We show in these assays that although relevant for the HCV life cycle SEC14L2 is not a reliable predictor of HCV replication fitness. Furthermore we show evidence for a different susceptibility to lipid peroxidation from different genotypes which argues in favour of different mechanisms from HCV to cope with host cell ROS, which is compatible with previous reports where different HCV genotypes would differentially interact with the host lipid metabolism.