2013 Fiscal Year Final Research Report
The role of lipid metabolism on HCV proliferation
Project/Area Number |
22249012
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Virology
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Research Institution | Research Institute, International Medical Center of Japan (2012-2013) Chiba Institute of Technology (2010-2011) |
Principal Investigator |
SHIMOTOHNO Kunitada 独立行政法人国立国際医療研究センター, その他部局等, その他 (10000259)
|
Project Period (FY) |
2010-05-31 – 2014-03-31
|
Keywords | ウイルス / 感染症 / C型肝炎ウイルス / 脂質 / 癌 / リポ蛋白質 |
Research Abstract |
Patients with chronic hepatitis C often develop steato-hepatitis. Abnormality of liver metabolism, often caused by activation of liver metabolism, in HCV infected liver is high, but roles of such the high metabolic activation in the cells in regards to virus proliferation remains elusive. We analyzed the role of lipid as well as its metabolism on HCV production and found; (1) HCV core protein is involved in accumulation of lipid droplet in the infected cells, (2) HCV associates with lipoprotein component(s) which is important for virus infectivity, (3) in particular, apolipoprotein E (Apo-E) plays an important roles in virus infectivity, (4) lipoprotein lipase treatment abolished virus infectivity possibly by dissociation of Apo-E from virus particle, (5) HCV infectivity is influenced by Apo-E isoforms; Apo-E3 and –E4 isoforms show high infectivity and Apo-E2 low. We also found a new lipoprotein receptor, VLDLR, for HCV entry.
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[Journal Article] Self-enhancement of hepatitis C virus replication by promotion of specific sphingolipid biosynthesis2012
Author(s)
Hirata Y, Ikeda K, Sudoh M, Tokunaga Y, Suzuki A, Weng L, Ohta M, Tobita Y, Okano Ozeki K, Kawasaki K, Tsukuda T, Katsume A, Aoki Y, Umehara T, Sekiguchi S, Toyoda T, Shimotohno K, Soga T, Nishijima M, Taguchi R, Kohara M
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Journal Title
PLoS Pathog
Volume: 8(8)
Pages: e1002860
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[Journal Article] Dysregulation of IFN system can lead to poor response to pegylated interferon and ribavirin therapy in chronic hepatitis C2011
Author(s)
Onomoto K, Morimoto S, Kawaguchi T, Toyoda H, Tanaka M, Kuroda M, Uno K, Kumada T, Matsuda F, Shimotohno K, Fujita T, Murakami Y
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Journal Title
PLoS One
Volume: 6(5)
Pages: e19799
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[Journal Article] Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B2011
Author(s)
Morohashi K, Sahara H, Watashi K, Iwabata K, Sunoki T, Kuramochi K, Takakusagi K, Miyashita H, Sato N, Tanabe A, Shimotohno K, Kobayashi S, Sakaguchi K, Sugawara F
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Journal Title
PLoS One
Volume: 6(4)
Pages: e18285
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[Journal Article] Infectivity of hepatitis C virus is influenced by association with apolipoprotein E isoforms2011
Author(s)
Hishiki T, Shimizu Y, Tobita R, Sugiyama K, Ogawa K, Funami K, Ohsaki Y, Fujimoto T, Takaku H, Wakita T, Baumert TF, Miyanari Y, Shimotohno K
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Journal Title
J Virol
Volume: 84(22)
Pages: 12048-12057
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