Alternative endocytosis pathway for productive entry of hepatitis C virus

Mami Matsuda, Ryosuke Suzuki, Chikako Kataoka, Koichi Watashi, Hideki Aizaki, Nobuyuki Kato, Yoshiharu Matsuura, Tetsuro Suzuki, Takaji Wakita

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 bafilomycin A1, reduced infection in Huh-7 and Huh7.5.1 cells, suggesting that HCV entered both cell types via receptor-mediated, pHdependent 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 (Arf6), 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 dynaminindependent in Hep3B/miR122 cells. Collectively, these data indicated that HCV entered different target cells through different entry routes.

Original languageEnglish
Pages (from-to)2658-2667
Number of pages10
JournalJournal of General Virology
Volume95
DOIs
Publication statusPublished - Dec 1 2014

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Endocytosis
Hepacivirus
Clathrin
Dynamin II
p21-Activated Kinases
Virus Internalization
Infection
Hepatocytes
Clathrin Heavy Chains
Claudin-1
Dynamins
Caveolin 1
Caveolae
Cell Communication
Virion
Cell Culture Techniques

ASJC Scopus subject areas

  • Virology
  • Medicine(all)

Cite this

Matsuda, M., Suzuki, R., Kataoka, C., Watashi, K., Aizaki, H., Kato, N., ... Wakita, T. (2014). Alternative endocytosis pathway for productive entry of hepatitis C virus. Journal of General Virology, 95, 2658-2667. https://doi.org/10.1099/vir.0.068528-0

Alternative endocytosis pathway for productive entry of hepatitis C virus. / Matsuda, Mami; Suzuki, Ryosuke; Kataoka, Chikako; Watashi, Koichi; Aizaki, Hideki; Kato, Nobuyuki; Matsuura, Yoshiharu; Suzuki, Tetsuro; Wakita, Takaji.

In: Journal of General Virology, Vol. 95, 01.12.2014, p. 2658-2667.

Research output: Contribution to journalArticle

Matsuda, M, Suzuki, R, Kataoka, C, Watashi, K, Aizaki, H, Kato, N, Matsuura, Y, Suzuki, T & Wakita, T 2014, 'Alternative endocytosis pathway for productive entry of hepatitis C virus', Journal of General Virology, vol. 95, pp. 2658-2667. https://doi.org/10.1099/vir.0.068528-0
Matsuda, Mami ; Suzuki, Ryosuke ; Kataoka, Chikako ; Watashi, Koichi ; Aizaki, Hideki ; Kato, Nobuyuki ; Matsuura, Yoshiharu ; Suzuki, Tetsuro ; Wakita, Takaji. / Alternative endocytosis pathway for productive entry of hepatitis C virus. In: Journal of General Virology. 2014 ; Vol. 95. pp. 2658-2667.
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