Journal
VIROLOGY
Volume 422, Issue 2, Pages 377-385Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2011.11.009
Keywords
Hrs; ESCRT; HCV
Categories
Funding
- JSPS
- MEXT KAKENHI [21590517, 19059001, 22790630]
- Ministry of Health, Labour and Welfare
- Takeda Medical Research Foundation
- Grants-in-Aid for Scientific Research [21590517, 22790630, 19059001, 22590713] Funding Source: KAKEN
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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. (C) 2011 Elsevier Inc. All rights reserved.
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