title: Annexin A1 negatively regulates viral RNA replication of hepatitis C virus.
abstract: Persistent infection with hepatitis C virus (HCV) often causes chronic hepatitis, and then shows a high rate of progression to liver cirrhosis and hepatocellular carcinoma. To clarify the mechanism of the persistent HCV infection is considered to be important for the discovery of new target(s) for the development of anti-HCV strategies. In the present study, we found that the expression level of annexin A1 (ANXA1) in human hepatoma cell line Li23-derived D7 cells was remarkably lower than that in parental Li23 cells, whereas the susceptibility of D7 cells to HCV infection was much higher than that of Li23 cells. Therefore, we hypothesized that ANXA1 negatively regulates persistent HCV infection through the inhibition of viral RNA replication. The results revealed that HCV production was significantly inhibited without a concomitant reduction in the amount of lipid droplets in the D7 cells stably expressing exogenous ANXA1. Further, we demonstrated that ANXA1 negatively regulated the step of viral RNA replication rather than that of viral entry in human hepatocytes. These results suggest that ANXA1 would be a novel target for the development of anti-HCV strategies.
authors.affiliation: Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hiramoto
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Dansako
authors.forename: Midori
authors.initials: M
authors.lastname: Takeda
authors.forename: Shinya
authors.initials: S
authors.lastname: Satoh
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Masanori
authors.initials: M
authors.lastname: Ikeda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kato
mesh_terms: D017305:Annexin A1 / Q000235:genetics / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D004198:Disease Susceptibility / Q000503:physiopathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000821:virology; D012367:RNA, Viral / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*
chemical_list: D017305:Annexin A1; D012367:RNA, Viral