GENETIC DIVERSITY OF SIMIAN RETROVIRUSES

猿猴逆转录病毒的遗传多样性

• 批准号: 6453675
• 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: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6453675
• 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).

D型D型逆转录病毒是获得猿猴的原因 亚洲生物医学研究社区的免疫缺陷综合症 猕猴，可以用作模型系统，以理解 信封（Env）糖蛋白基因多样性在调节细胞质量方面 并发作艾滋病发病机理。 逆转录病毒经历高频 其ENV基因中的突变，并受到选择压力 这导致出现新的病理预防 变体。 我们已经分子克隆并测序了完整 D型氨基酸逆转录病毒（SRV血清群2; D2/RHE/OR）的基因组和 从恒河猕猴中回收的变体病毒 带有典型的血清群2病毒。 传染性分子基因组 D2/rhe/或一个变体的D2/Rhe/或/V1已恢复。 构建了相互的嵌合病毒以分析 病毒基因组决定因素对体外做出的贡献 淋巴样细胞的感染性。 这些实验表明 D2/RHE/或感染T细胞线的能力降低，尤其是 HUT-78和MT细胞，以及多个病毒基因组决定因素 影响向潮流。 另外，我们有分离的感染分子 血清群4（D4/CYN/CA）和血清群5（D5/RHE/OR）SRV的克隆。 这些其他基因组克隆的完整序列分析表明 血清群4和5 srvs在遗传上均依赖于所有人 先前表征的血清群。 在最近的工作中，使用 酵母两个混合动力系统，我们现在正在尝试 分子粘液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 血清群2、4和5 SRV的完整序列分析具有 提供了有关遗传多样性的重要信息 猿猴逆转录病毒。 这些分子克隆和电势 SRV受体和细胞信号分子的鉴定将 为将来的Struc提供必要的分子试剂 功能功能和细胞/组织的朝向主义实验。 资金 RR00163/AIDS补充项目8 Publications Moudgil T，Machida CA。 酵母的两杂化系统鉴定分子与 Simian逆转录病毒ENV基因产品。 在16年年度计划中 艾滋病的非人类灵长类动物模型研讨会（在佐治亚州亚特兰大举行， 1998年10月7日至10日）（摘要78）。