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

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790630
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Miyagi Cancer Center Research Institute
• Principal Investigator: TAMAI Keiichi 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん先進治療開発研究部, 主任研究員 (40509262)
• Project Period (FY): 2010 – 2011
• Keywords: ESCRT / Hrs / exosomes / HCV

Research Abstract

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. 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.

Research Products

• [Journal Article] Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway (2012)
  • Author(s): K. Tamai, M. Shiina, N. Tanaka, T. Nakano, A. Yamamoto, Y. Kondo, E. Kakazu, J. Inoue, K. Fukushima, K. Sano, Y. Ueno, T. Shimosegawa, K. Sugamura
  • Journal Title: Virology Volume: 422 Pages: 377-385
  • DOI: DOI:10.1016/j.virol.2011.11.009
• [Journal Article] Powered, The AAA-ATPase VPS4 Regulates Extracellular Secretion and Lysosomal Targeting ofα-Synuclein (2011)
  • Author(s): Takafumi Hasegawa, M. Konno, T. Baba, N. Sugeno, A. Kikuchi, M. Kobayashi, E. Miura, N. Tanaka, K. Tamai, K. Furukawa, H. Arai, F. Mori, K. Wakabayashi, M. Aoki, Y. Itoyama, A. Takeda
  • Journal Title: PLoS One
• [Journal Article] AMSH is required to degrade ubiquitinated proteins in the central nervous system (2011)
  • Author(s): S. Suzuki, K. Tamai, M. Watanabe, M. Kyuuma, M. Ono, K. Sugamura, N. Tanaka
  • Journal Title: Biochem Biophys Res Commun Volume: 408 Pages: 582-588
  • DOI: DOI:10.1016/j.bbrc.2011.04.065
• [Journal Article] Lymphotropic HCV strain can infect human primary naive CD4+cells and affect their proliferation and IFN-gamma secretion activity (2011)
  • Author(s): Y. Kondo, Y. Ueno, E. Kakazu, K. Kobayashi, M. Shiina, K. Tamai, K. Machida, J. Inoue, Y. Wakui, K. Fukushima, N. Obara, O. Kimura, T. Shimosegawa
  • Journal Title: J Gastroenterol Volume: 46 Pages: 232-241
  • DOI: DOI:10.1007/s00535-010-0297-2
• [Journal Article] Plasma L-cystine/L-glutamate imbalance increases tumor necrosis factor-alpha from CD14+circulating monocytes in patients with advanced cirrhosis (2011)
  • Author(s): E. Kakazu, Y. Ueno, Y. Kondo, J. Inoue, M. Ninomiya, O. Kimura, Y. Wakui, K. Fukushima, K. Tamai, T. Shimosegawa
  • Journal Title: PLoS One Volume: 6 Pages: 23402
  • DOI: DOI:10.1371/journal.pone.0023402
• [Journal Article] Four-year study of lamivudine and adefovir combination therapy in lamivudine-resistant hepatitis B patients : influence of hepatitis B virus genotype and resistance mutation pattern (2011)
  • Author(s): J. Inoue, Y. Ueno, Y. Wakui, H. Niitsuma, K. Fukushima, Y. Yamagiwa, M. Shiina, Y. Kondo, E. Kakazu, K. Tamai, N. Obara, T. Iwasaki, T. Shimosegawa
  • Journal Title: J Viral Hepat Volume: 18 Pages: 206-215
  • DOI: DOI:10.1111/j.1365-2893.2010.01301.x
• [Journal Article] Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein (2010)
  • Author(s): K. Tamai, N. Tanaka, T. Nakano, E. Kakazu, Y. Kondo, J. Inoue, M. Shiina, K. Fukushima, T. Hoshino, K. Sano, Y. Ueno, T. Shimosegawa, K. Sugamura
  • Journal Title: Biochem Biophys Res Commun Volume: 399 Pages: 384-390
  • DOI: DOI:10.1016/j.bbrc.2010.07.083
• [Journal Article] Possible involvement and the mechanisms of excess trans-fatty acid consumption in severe NAFLD in mice (2010)
  • Author(s): N. Obara, K. Fukushima, Y. Ueno, Y. Wakui, O. Kimura, K. Tamai, E. Kakazu, J. Inoue, Y. Kondo, N. Ogawa, K. Sato, T. Tsuduki, K. Ishida, T. Shimosegawa
  • Journal Title: J Hepatol Volume: 53 Pages: 326-334
  • DOI: DOI:10.1016/j.jhep.2010.02.029
• [Journal Article] Hepatitis B virus replication could enhance regulatory T cell activity by producing soluble heat shock protein 60 from hepatocytes (2010)
  • Author(s): Y. Kondo, Y. Ueno, K. Kobayashi, E. Kakazu, M. Shiina, J. Inoue, K. Tamai, Y. Wakui, Y. Tanaka, M. Ninomiya, N. Obara, K. Fukushima, M. Ishii, T. Kobayashi, H. Niitsuma, S. Kon, T. Shimosegawa
  • Journal Title: J Infect Dis Volume: 202 Pages: 202-213
  • DOI: DOI:10.1086/653496