title: Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway.
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.
authors.affiliation: Division of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, Natori 981-1293, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tamai
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shiina
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Kondo
authors.forename: Eiji
authors.initials: E
authors.lastname: Kakazu
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.forename: Koji
authors.initials: K
authors.lastname: Fukushima
authors.forename: Kouichi
authors.initials: K
authors.lastname: Sano
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugamura
mesh_terms: D001343:Autophagy; D002460:Cell Line; D002462:Cell Membrane; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism; D014758:Viral Core Proteins / Q000378:metabolism*; D019065:Virus Assembly / Q000502:physiology
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; D012367:RNA, Viral; D014758:Viral Core Proteins; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate