title: ARF1 and GBF1 generate a PI4P-enriched environment supportive of hepatitis C virus replication.
abstract: Cellular levels of phosphatidylinositol 4-phosphate (PI4P) have been shown to be upregulated during RNA replication of several viruses, including the HCV replicon model. However, whether PI4P is required in an infectious HCV model remains unknown. Moreover, it is not established whether the host transport machinery is sequestered by the generation of PI4P during HCV infection. Here we found that PI4P was enriched in HCV replication complexes when Huh7.5.1 cells were infected with JFH1. HCV replication was inhibited upon overexpression of the PI4P phosphatase Sac1. The PI4P kinase PI4KIIIβ was also found to be required for HCV replication. Moreover, the vesicular transport proteins ARF1 and GBF1 colocalized with PI4KIIIβ and were both required for HCV replication. During authentic HCV infection, PI4P plays an integral role in virus replication.
authors.affiliation: Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Leiliang
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Hong
authors.forename: Wenyu
authors.initials: W
authors.lastname: Lin
authors.forename: Run-Xuan
authors.initials: RX
authors.lastname: Shao
authors.forename: Kaku
authors.initials: K
authors.lastname: Goto
authors.forename: Victor W
authors.initials: VW
authors.lastname: Hsu
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D018129:Phosphatidylinositol Phosphates / Q000032:analysis / Q000096:biosynthesis*; D012367:RNA, Viral / Q000096:biosynthesis; D033921:Vesicular Transport Proteins; D014779:Virus Replication
chemical_list: C120445:GBF1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D018129:Phosphatidylinositol Phosphates; D012367:RNA, Viral; D033921:Vesicular Transport Proteins; C037178:phosphatidylinositol 4-phosphate; D020823:ADP-Ribosylation Factor 1