Establishment of mouse-directed HCV infection models

小鼠HCV感染模型的建立

• 批准号: 22659145
• 负责人: SAKAMOTO Naoya
• 金额: $ 2.04万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659145/
• 关键词: HCV; CD81; HCV-JFH1培養系

In our present study, we constructed two fluorescence protein-tagged recombinant JFH1 virus clones, JFH1-EYFP and JFH1-AsRed, as well as two corresponding clones with adaptive mutations, JFH1-EYFP mutant and JFH1-AsRed mutant, that and were as effective as JFH1 in producing infectious virus particles, and investigated their viral infection life cycles. After infection of the fluorescence-tagged mutant viruses, infected cells increased exponentially. In cells, EYFP or AsRed and NS5A were expressed as a fusion protein and co-localized in core proteins. The rate of the cell. cell spread was dependent on the cell densities with a maximum of 102. 5/day. Treatment of cells with interferon or a protease inhibitor suppressed expansion of virus-positive cells. Taken together, these results indicate that fluorescence-tagged HCV is a useful tool to study virus infection life cycles and to assist in the search for novel antiviral compounds.

在本研究中，我们构建了两个荧光蛋白标记的重组JFH1病毒克隆JFH1-EYFP和JFH1-AsRed，以及相应的两个具有适应性突变的克隆JFH1-EYFP突变体和JFH1-Asred突变体，它们在产生感染性病毒颗粒方面与JFH1一样有效，并对它们的感染生活史进行了研究。感染荧光标记突变病毒后，感染细胞呈指数增长。在细胞中，EYFP或AsRed与NS5A以融合蛋白的形式表达，并共定位于核心蛋白中。单元格的速率。细胞扩散依赖于细胞密度，最大为102。5个/天。用干扰素或蛋白水解酶抑制剂处理细胞可抑制病毒阳性细胞的扩张。综上所述，这些结果表明，荧光标记的丙型肝炎病毒是一个有用的工具来研究病毒感染的生命周期，并帮助寻找新的抗病毒化合物。

项目成果

Serum interleukin-6 levels correlate with resistance to treatment of chronic hepatitis C infection with pegylated-interferon-alpha2b plus ribavirin

血清白细胞介素 6 水平与聚乙二醇干扰素 α2b 加利巴韦林治疗慢性丙型肝炎感染的耐药性相关

• 发表时间: 2011
• 期刊: Antivir Ther
• 影响因子: 1.2
• 作者: Ueyama M;Nakagawa M;Sakamoto N;et al.
• 通讯作者: et al.

Mutations in the interferon sensitivity determining region of HCV, age and total ribavirin dose is an independent predictor of relapse among early virological responders to peg-interferon plus ribavirin therapy

HCV 干扰素敏感性决定区、年龄和利巴韦林总剂量的突变是对聚乙二醇干扰素联合利巴韦林治疗的早期病毒学应答者中复发的独立预测因素

• 发表时间: 2011
• 作者: Kurosaki M;Sakamoto N;Nakagawa M;et al.
• 通讯作者: et al.

Inhibition of HCV replication by a specific inhibitor of serin-arginine-rich protein kinase

富含丝氨酸-精氨酸的蛋白激酶的特异性抑制剂抑制 HCV 复制

• 发表时间: 2010
• 期刊: Antimicrob Agent Chemother
• 作者: Karakama Y;Sakamoto N;Itsui Y;Nakagawa M;Tasaka-Fujita M;Nishimura-Sakurai Y;Kakinuma S;Oooka S;Azuma S;Tsuchiya K;Onogi H;Hagiwara M;Watanabe M.
• 通讯作者: Watanabe M.

A new method for induced fit docking (GENIUS) and its application to virtual screening of novel HCV NS3-4A protease inhibitors

诱导拟合对接新方法（GENIUS）及其在新型HCV NS3-4A蛋白酶抑制剂虚拟筛选中的应用

• DOI: 10.1016/j.bmc.2011.09.023
• 发表时间: 2011
• 期刊: Bioorganic & Medicinal Chemistry
• 影响因子: 3.5
• 作者: Takaya D;Sakamoto N;et al.
• 通讯作者: et al.

A high-content screening assay using infectious fluorescence-tagged hepatitis C virus reveals candidates fo rsmall molecule inhibitors of viral entry

使用传染性荧光标记丙型肝炎病毒的高内涵筛选测定揭示了病毒进入小分子抑制剂的候选物

• 发表时间: 2011
• 作者: Kusano-Kitazume A;Sakamoto N;Okuno Y;Yamamoto M;Sekine-Osajima Y;Nakagawa M;Kakinuma S;Kiyohashi K;Nitta S;Murakawa M;Hagiwara M;Watanabe M
• 通讯作者: Watanabe M