Identification of GBF1 as a Cellular Factor Required for Hepatitis C Virus RNA Replication

摘要: In infected cells, hepatitis C virus (HCV) induces the formation of membrane alterations referred to as membranous webs, which are sites RNA replication. addition, HCV replication also occurs in smaller structures that associated with endoplasmic reticulum. However, cellular mechanisms involved complexes remain largely unknown. Here, we used brefeldin A (BFA) investigate infection. BFA acts on cell membranes by interfering activation several members family ADP-ribosylation factors (ARF), can lead a wide range inhibitory actions membrane-associated secretory and endocytic pathways. Our data show is highly sensitive BFA. Individual knockdown targets using interference use specific pharmacological inhibitor identified GBF1, guanine nucleotide exchange factor for small GTPases ARF family, host critically Furthermore, overexpression BFA-resistant GBF1 mutant rescued BFA-treated indicating BFA-sensitive required Finally, immunofluorescence electron microscopy analyses indicated does not block web-like induced expression proteins nonreplicative context, suggesting probably but, rather, their activity. Altogether, our results highlight functional connection between early pathway