Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway

Keiichi Tamai, Masaaki Shiina, Nobuyuki Tanaka, Takashi Nakano, Akitsugu Yamamoto, Yasuteru Kondo, Eiji Kakazu, Jun Inoue, Koji Fukushima, Kouichi Sano, Yoshiyuki Ueno, Tooru Shimosegawa, Kazuo Sugamura

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

The molecular mechanisms of assembly and budding of hepatitis C virus (HCV) remain poorly understood. The budding of several enveloped viruses requires an endosomal sorting complex required for transport (ESCRT), which is part of the cellular machinery used to form multivesicular bodies (MVBs). Here, we demonstrated that Hrs, an ESCRT-0 component, is critical for the budding of HCV through the exosomal secretion pathway. Hrs depletion caused reduced exosome production, which paralleled with the decrease of HCV replication in the host cell, and that in the culture supernatant. Sucrose-density gradient separation of the culture supernatant of HCV-infected cells revealed the co-existence of HCV core proteins and the exosome marker. Furthermore, both the core protein and an envelope protein of HCV were detected in the intraluminal vesicles of MVBs. These results suggested that HCV secretion from host cells requires Hrs-dependent exosomal pathway in which the viral assembly is also involved.

Original languageEnglish
Pages (from-to)377-385
Number of pages9
JournalVirology
Volume422
Issue number2
DOIs
Publication statusPublished - 2012 Jan 20

Keywords

  • ESCRT
  • HCV
  • Hrs

ASJC Scopus subject areas

  • Virology

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