論文

査読有り
2014年12月

Alternative endocytosis pathway for productive entry of hepatitis C virus

JOURNAL OF GENERAL VIROLOGY
  • Mami Matsuda
  • ,
  • Ryosuke Suzuki
  • ,
  • Chikako Kataoka
  • ,
  • Koichi Watashi
  • ,
  • Hideki Aizaki
  • ,
  • Nobuyuki Kato
  • ,
  • Yoshiharu Matsuura
  • ,
  • Tetsuro Suzuki
  • ,
  • Takaji Wakita

95
Pt 12
開始ページ
2658
終了ページ
2667
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1099/vir.0.068528-0
出版者・発行元
SOC GENERAL MICROBIOLOGY

Previous studies have shown that hepatitis C virus (HCV) enters human hepatic cells through interaction with a series of cellular receptors, followed by clathrin-mediated, pH-dependent endocytosis. Here, we investigated the mechanisms of HCV entry into multiple HCV-permissive human hepatocyte-derived cells using trans-complemented HCV particles (HCVtcp). Knockdown of CD81 and claudin-1, or treatment with bafilonnycin A1, reduced infection in Huh-7 and Huh7.5.1 cells, suggesting that HCV entered both cell types via receptor-mediated, pH-dependent endocytosis. Interestingly, knockdown of the clathrin heavy chain or dynamin-2 (Dyn2), as well as expression of the dominant-negative form of Dyn2, reduced infection of Huh-7 cells with HCVtcp, whereas infectious entry of HCVtcp into Huh7.5.1 cells was not impaired. Infection of Huh7.5.1 cells with culture-derived HCV (HCVcc) via a clathrin-independent pathway was also observed. Knockdown of caveolin-1, ADP-ribosylation factor 6 (Aria flotillin, p21-activated kinase 1 (PAK1) and the PAK1 effector C-terminal binding protein 1 of E1A had no inhibitory effects on HCVtcp infection into Huh7.5.1 cells, thus suggesting that the infectious entry pathway of HCV into Huh7.5.1 cells was not caveolae-mediated, or Arf6- and flotillin-mediated endocytosis and macropinocytosis, but rather may have occurred via an undefined endocytic pathway. Further analysis revealed that HCV entry was clathrin- and dynamin-dependent in ORL8c and HepCD81/miR122 cells, but productive entry of HCV was clathrin- and dynamin-independent in Hep3B/miR122 cells. Collectively, these data indicated that HCV entered different target cells through different entry routes.

リンク情報
DOI
https://doi.org/10.1099/vir.0.068528-0
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25096815
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000350943800008&DestApp=WOS_CPL
ID情報
  • DOI : 10.1099/vir.0.068528-0
  • ISSN : 0022-1317
  • eISSN : 1465-2099
  • PubMed ID : 25096815
  • Web of Science ID : WOS:000350943800008

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