Study on infection and maturation mechanisms of hepatitis C virus and its host response.

丙型肝炎病毒感染、成熟机制及其宿主反应研究。

• 批准号: 15209017
• 负责人: MATSUURA Yoshiharu
• 金额: $ 28.37万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15209017/
• 关键词: HCV; Infection Mechanisms; Receptor; Pseudotype Virus; Envelope Protein; リセプター; プロテアソーム

To examine the molecular mechanisms of hepatitis C virus (HCV) infection, we prepared pseudotype viruses bearing unmodified HCV envelope proteins based on vesicular stomatitis virus (HCVpv) in both 293T and CHO cells. HCVpv generated in 293T cells (HCVpv/293T) exhibited a high infectivity to Huh7 cells but not to HepG2 cells. The infection of HCVpv/293T to Huh7 cells was neutralized by anti-hCD81 antibody, as reported for the pseudotype viruses based on murine leukemia virus (HCVpp) generated in 293T cells. In contrast, HCVpv generated in CHO cells (HCVpv/CHO) exhibited a high infectivity to hCD81-negative HepG2 cells and a weak infectivity to Huh7 cells. These results indicate that HCVpv/293T and HCVpv/CHO exhibit hCD81-dependent and -independent infectivity, respectively. Sera taken from chronic hepatitis C patients efficiently neutralized HCVpv/293T infection, as reported for HCVpp infection, whereas only a slight inhibition of HCVpv/CHO infection was observed. Naturally occurring HCV particles in serum taken from a hepatitis C patient during the window period of infection also exhibited binding to both Huh7 and HepG2 cells. In conclusion, these results indicate that the cell tropism of the HCV pseudotype viruses is determined by the producing cell lines, and that at least two types of HCV particles bearing similar properties to the pseudotype viruses exhibiting hCD81-dependent and -independent infection circulate in the serum of hepatitis C patients.

为了研究丙型肝炎病毒（HCV）感染的分子机制，我们在293T和CHO细胞中制备了基于水泡性口炎病毒（HCVpv）的携带未修饰的HCV包膜蛋白的假病毒。293T细胞中产生的HCVpv （HCVpv/293T）对Huh7细胞具有较高的感染性，但对HepG2细胞没有感染性。HCVpv/293T对Huh7细胞的感染被抗hcd81抗体所中和，报道了在293T细胞中产生的基于小鼠白血病病毒（HCVpp）的伪病毒。相反，CHO细胞中生成的HCVpv （HCVpv/CHO）对hcd81阴性的HepG2细胞具有较高的感染性，对Huh7细胞的感染性较弱。这些结果表明，HCVpv/293T和HCVpv/CHO分别表现出hcd81依赖性和非依赖性的感染性。慢性丙型肝炎患者的血清有效地中和了HCVpv/293T感染，正如HCVpp感染所报道的那样，而仅观察到对HCVpv/CHO感染的轻微抑制。在感染窗口期从丙型肝炎患者血清中提取的自然存在的HCV颗粒也显示出与Huh7和HepG2细胞的结合。综上所述，这些结果表明，HCV假病毒的细胞趋向性是由产生的细胞系决定的，并且至少有两种与hcd81依赖性和非依赖性假病毒具有相似特性的HCV颗粒在丙型肝炎患者的血清中循环。

项目成果

Characterization of HCV-like particles produced in a human hepatoma cell line by a recombinant baculovirus.

重组杆状病毒在人肝癌细胞系中产生的 HCV 样颗粒的表征。

• 发表时间: 2006
• 期刊: BBRC 340
• 作者: Suenaga;N. 他3名;Yoshiki Murakumo;Matsuo E.
• 通讯作者: Matsuo E.

Mechanism of hepatitis C virus infection.

丙型肝炎病毒感染的机制。

• 发表时间: 2003
• 期刊: Antiviral Chemistry and Chemotherapy 14
• 作者: Abe;M.;Matsushita;N.;Shimazu;R.;Tada;M.;Gokon;N.;Nishio;K.;Handa;H.;Moriishi K.
• 通讯作者: Moriishi K.

Essential elements of the capsid protein for self-assembly into empty virus-like particles of hepatitis E virus

• DOI: 10.1128/jvi.79.20.12999-13006.2005
• 发表时间: 2005-10-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Li, TC;Takeda, N;Cheng, RH
• 通讯作者: Cheng, RH

Evidence for an alternative topology of the El envelope glycoprotein of hepatitis C virus.

丙型肝炎病毒 El 包膜糖蛋白替代拓扑结构的证据。

• 发表时间: 2004
• 期刊: Virus Research 105
• 作者: 中崎 満浩;Yoshinori Kodama;Migliaccio C.T.
• 通讯作者: Migliaccio C.T.

Aizaki H.: "Production and release of infectious hepatitis C virus from human liver cell cultures in the three-dimensional radial-flow bioreactor"Virology. 134. 16-25 (2003)

Aizaki H.：“在三维径向流生物反应器中从人肝细胞培养物中产生和释放传染性丙型肝炎病毒”病毒学。