The role of lipid metabolism on HCV proliferation

脂质代谢对HCV增殖的作用

• 批准号: 22249012
• 负责人: SHIMOTOHNO Kunitada
• 金额: $ 29.87万
• 依托单位: Research Institute, International Medical Center of Japan (2012-2013)Chiba Institute of Technology (2010-2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010-05-31 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22249012/
• 关键词: ウイルス; 感染症; C型肝炎ウイルス; 脂質; 癌; リポ蛋白質; 持続感染; VLDL受容体; アポリポ蛋白質E; 低酸素環境; VLDLR; LDLR; 感染; 受容体; 脂肪滴; 脂肪症; アポリポ蛋白質; 複製

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.

慢性丙型肝炎患者常发展为脂肪性肝炎。在丙型肝炎病毒感染的肝脏中，肝脏代谢异常，通常是由肝脏代谢激活引起的，但这种高代谢激活在细胞中与病毒增殖有关的作用仍不清楚。我们分析了脂质及其代谢在丙型肝炎病毒产生中的作用，发现：(1)丙型肝炎病毒核心蛋白参与了感染细胞中脂滴的积累，(2)丙型肝炎病毒与脂蛋白成分(S)有关，脂蛋白E(Apo-E)对病毒的传染性起重要作用，(4)脂蛋白脂肪酶处理可能通过将Apo-E从病毒颗粒中解离而取消病毒的感染性，(5)丙型肝炎病毒的感染性受Apo-E亚型的影响，Apo-E3和-E4亚型表现为高传染性，Apo-E2低。我们还发现了一种新的脂蛋白受体，VLDLR，用于丙型肝炎病毒的进入。

项目成果

Lipoprotein components associated with hepatitis C virus is essential for virus infectivity

与丙型肝炎病毒相关的脂蛋白成分对于病毒感染性至关重要

• 发表时间: 2011
• 期刊: Current Opinion in Virology
• 影响因子: 5.9
• 作者: Shimizu Y;Hishiki T;Ujino S;Sugiyama K;Funmi K;Shimotohno K
• 通讯作者: Shimotohno K

Critical role of interferon-α constitutively produced in human hepatocytes in response to RNA virus infection.

• DOI: 10.1371/journal.pone.0089869
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Tsugawa Y;Kato H;Fujita T;Shimotohno K;Hijikata M
• 通讯作者: Hijikata M

Lipoprotein lipase and hepatic triglyceride lipase reduce the infectivity of hepatitis C virus (HCV) through their catalytic activities on HCV-associated lipoproteins.

脂蛋白脂肪酶和肝甘油三酯脂肪酶通过其对丙型肝炎病毒（HCV）相关脂蛋白的催化活性来降低丙型肝炎病毒（HCV）的感染性。

• 发表时间: 2010
• 期刊: Virology. 407(1)
• 作者: Shimizu Y;Hishiki T;Sugiyama K;Ogawa K;Funami K;Kato A;Ohsaki Y;Fujimoto T;Takaku H;Shimotohno K.
• 通讯作者: Shimotohno K.

C型肝炎ウイルス研究の新知見 医学のあゆみ

丙型肝炎病毒研究的新发现医学史

• 发表时间: 2010
• 作者: Senga K.;Mostov K. E.;Mitaka T.;Miyajima A.;and Tanimizu N.;下遠野 邦忠
• 通讯作者: 下遠野 邦忠

PML tumor suppressor protein is required for HCV production

• DOI: 10.1016/j.bbrc.2012.11.108
• 发表时间: 2013-01-11
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Kuroki, Misao;Ariumi, Yasuo;Kato, Nobuyuki
• 通讯作者: Kato, Nobuyuki