GENETIC DIVERSITY OF SIMIAN RETROVIRUSES

猿逆转录病毒的遗传多样性

• 批准号: 6592299
• 负责人: CURTIS A MACHIDA
• 金额: $ 11.11万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6592299
• 关键词: AIDS; Mammalia; animal tissue; biotechnology; communicable diseases; immunology; inflammation; lymphatic system; virus

The simian type D retroviruses are the cause of Simian Acquired Immunodeficiency Syndrome in biomedical research communities in Asian macaques, and can serve as model systems in understanding the role of envelope (env) glycoprotein gene diversity in modulating cell tropism and onset in AIDS pathogenesis. Retroviruses undergo high-frequency mutations in their env genes and are subjected to selection pressures that result in the appearance of new pathologically-advantaged variants. We have molecularly-cloned and sequenced the complete genomes of a type D simian retrovirus (SRV serogroup 2; D2/RHE/OR) and variant viruses recovered from rhesus macaques endemically infected with the prototypical serogroup 2 virus. Infectious molecular genomes of D2/RHE/OR and one variant, D2/RHE/OR/V1, have been recovered. Reciprocal chimeric viruses were constructed to analyze the contributions made by viral genomic determinants to in vitro infectivity of lymphoid cells. These exp eriments indicate that D2/RHE/OR has a reduced ability to infect T-cell lines, especially Hut-78 and MT-cells, and that multiple viral genomic determinants influence tropism. In addition, we have isolated infectious molecular clones of serogroup 4 (D4/CYN/CA) and serogroup 5 (D5/RHE/OR) SRVs. Complete sequence analyses of these additional genomic clones indicate that serogroups 4 and 5 SRVs are genetically-distinct from all previously characterized serogroups. In recent work, with the use of the yeast two hybrid system, we are now attempting to molecularly-clone the genes encoding env-interactive proteins, including potential SRV receptor and cell signaling molecules. The complete sequence analyses of the serogroup 2, 4 and 5 SRVs has provided important information concerning the genetic diversity of the simian retroviruses. These molecular clones and the potential identification of the SRV receptor and cell signaling molecules will provide the necessary molecular reagents for future struc ture-function and cell/tissue tropism experiments. FUNDING RR00163/AIDS Supplement Project 8 PUBLICATIONS Moudgil T, Machida CA. Yeast two-hybrid system identification of molecules interacting with simian retroviral env gene products. In Program of the Sixteen Annual Symposium on Nonhuman Primate Models for AIDS (held in Atlanta, GA, October 7-10, 1998) (abstract 78).

猿猴 D 型逆转录病毒是导致猿猴获得性遗传病的原因 亚洲生物医学研究界的免疫缺陷综合症 猕猴，并且可以作为模型系统来理解 调节细胞趋向性的包膜（env）糖蛋白基因多样性 和艾滋病发病机制中的发病机制。 逆转录病毒经历高频 env 基因突变并受到选择压力 导致新的病理优势的出现 变种。 我们已经对完整的分子克隆和测序 D 型猿猴逆转录病毒（SRV 血清组 2；D2/RHE/OR）的基因组和 从受地方性感染的恒河猴中回收的变异病毒 与典型血清组 2 病毒一起。 传染性分子基因组 D2/RHE/OR 和一种变体 D2/RHE/OR/V1 已被回收。 构建相互嵌合病毒来分析 病毒基因组决定因素对体外的贡献 淋巴细胞的传染性。 这些实验表明 D2/RHE/OR 感染 T 细胞系的能力降低，尤其是 Hut-78 和 MT 细胞，以及多种病毒基因组决定因素 影响取向。 此外，我们还分离出了传染性分子 血清组 4 (D4/CYN/CA) 和血清组 5 (D5/RHE/OR) SRV 的克隆。 这些额外基因组克隆的完整序列分析表明 血清群 4 和 5 SRV 在基因上与所有血清群不同 先前表征的血清群。 在最近的工作中，使用 酵母两种混合系统，我们现在正在尝试 分子克隆编码环境相互作用蛋白的基因， 包括潜在的SRV受体和细胞信号分子。 这 血清组 2、4 和 5 SRV 的完整序列分析 提供了有关遗传多样性的重要信息 猿猴逆转录病毒。 这些分子克隆和潜力 SRV 受体和细胞信号分子的鉴定将 为未来的结构提供必要的分子试剂 真实功能和细胞/组织向性实验。 资金 RR00163/艾滋病补充项目 8 出版物 Moudgil T, Machida CA。 酵母双杂交系统鉴定分子相互作用 猿猴逆转录病毒env基因产物。 在第十六届年度计划中 非人类灵长类艾滋病模型研讨会（在佐治亚州亚特兰大举行， 1998 年 10 月 7-10 日）（摘要 78）。