Analysis of lamivudine resistance acquisition by hepatitis B virus.

乙型肝炎病毒拉米夫定耐药性获得分析。

• 批准号: 13557049
• 负责人: CHAYAMA Kazuaki
• 金额: $ 8.32万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557049/
• 关键词: hepatitis B virus; HBs antigen; HBe antigen; HBV DNA; replication; core promoter; adefovir; lamivudine; YMDDvariant; HBV; real time PCR; whole genome; mutation; 薬剤耐性

Hepatitis B virus infection is a serious health problem worldwide. As the hepatitis B virus infects only humans and chimpanzees, establishment of reliable culture system is necessary to study this important pathogen. We cloned a fu11 length genotype C clone of the hepatitis B virus from a patient with a very mild hepatitis. About one and half genome was cloned into a plasmid vector. The 1.4 length clone was transfected to a HepG2 cell line. The resultant cell line produced HBs antigen, HBe antigen and HBV DNA to a supernatant. The titer of HBV DNA was 10^6-10^7 copy/ml. The production of the HBV DNA was reduced by incubation of lamivudine and interferons. The clones should be useful to further develop anti-hepatitis B virus agents and study biological properties of the hepatitis B virus.

乙型肝炎病毒感染是世界范围内的一个严重的健康问题。由于乙型肝炎病毒仅感染人类和黑猩猩，因此有必要建立可靠的培养系统来研究这种重要的病原体。我们从一名患有极轻度肝炎的患者身上克隆了 fu11 长度的 C 型乙型肝炎病毒克隆。大约一个半基因组被克隆到质粒载体中。将 1.4 长度克隆转染至 HepG2 细胞系。所得细胞系在上清液中产生HBs抗原、HBe抗原和HBV DNA。 HBV DNA滴度为10^6-10^7拷贝/ml。拉米夫定和干扰素的孵育可减少 HBV DNA 的产生。这些克隆应该有助于进一步开发抗乙型肝炎病毒药物和研究乙型肝炎病毒的生物学特性。

项目成果

K.Tsuboi, S.Tazuma, H.Ochi, Chayama K.: "Hydrophilic bile salts have a cyclosporine A-induced cholestasis through enhanced canalicular membrane fluidity and transporter activity."Hepatol Res. 25,1. 38-47 (2003)

K.Tsuboi、S.Tazuma、H.Ochi、Chayama K.：“亲水性胆汁盐通过增强小管膜流动性和转运蛋白活性，具有环孢菌素 A 诱导的胆汁淤积。”Hepatol Res。

T.Kameda, K.Haruma, Chayama K.et al.: "Significance of an exaggerated meal-stimulated gastrin response in pathogenesis of Helicobacter pylori-negative duodenalulcer."Dig Dis Sci. 48(4). 644-651 (2003)

T.Kameda、K.Haruma、Chayama K.等人：“在幽门螺杆菌阴性十二指肠溃疡发病机制中，膳食刺激的胃泌素反应过度的意义。”Dig Dis Sci。

J.Tanaka, H.Kumada, K.Ikeda, Chayama K.ほか7名: "Natural histories of hepatitis C virus infection in men and women simulated by the markov model"Journal of medical virology. 70,3. 378-386 (2003)

J.Tanaka、H.Kumada、K.Ikeda、Chayama K. 等 7 人：“马尔可夫模型模拟的男性和女性丙型肝炎病毒感染的自然史”医学病毒学杂志 70,3。 2003）

K.Nakai, S.Tazuma, T.Nishioka, Chayama K.: "Inhibition of cholesterol crystallization uder pilirubin deconjugation : partial characterization of mechanisms whereby infected bile accelerates pigment stone formation"Biochem Biophys Acta. 1632,1-3. 48-54 (20

K.Nakai、S.Tazuma、T.Nishioka、Chayama K.：“毛红素解结合对胆固醇结晶的抑制：感染胆汁加速色素结石形成机制的部分表征”Biochem Biophys Acta。

T.Kamada, K.Haruma, Chayama K.ほか7名: "Significance of an exaggerated meal-stimulated gastrin response in pathogenesis of Helicobacter pylori-negative duodenal ulcer"Dig Dis Sci. 48,4. 644-651 (2003)

T. Kamada、K. Haruma、Chayama K. 和其他 7 人：“幽门螺杆菌阴性十二指肠溃疡发病机制中夸大的膳食刺激胃泌素反应的意义”Dig Dis Sci 48,4 (2003)。