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型逆转录病毒是猿猴获得性疾病的原因 亚洲生物医学研究社区中的免疫缺陷综合征 猕猴，并可以作为模型系统来理解 调控细胞趋向性的包膜糖蛋白基因多样性 并在艾滋病发病机制中起病。逆转录病毒经历高频 它们env基因的突变，并受到选择压力的影响 这导致了新的病理优势的出现 变种。我们已经进行了分子克隆和测序 D型猴逆转录病毒(SRV血清组2；D2/RHE/OR)基因组和 从地方性感染恒河猴中发现变异病毒 与典型的血清组2病毒有关。感染性分子基因组 D2/RHE/OR和一个变种D2/RHE/OR/V1已被恢复。 构建了相互嵌合的病毒来分析 病毒基因组决定簇对体外研究的贡献 淋巴样细胞的传染性。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 血清群4(D4/Cyn/CA)和血清群5(D5/RHE/OR)SRV的克隆。 对这些额外的基因组克隆的完整序列分析表明 群4和群5的SRV在基因上是不同的 以前的特征是血清群。在最近的工作中，通过使用 酵母双杂交系统，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。这个 对血清组2、4和5的SRV的完整序列分析有 提供了有关该物种遗传多样性的重要信息 猿猴逆转录病毒。这些分子克隆和潜在的 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 真功能和细胞/组织趋向性实验。资金来源 RR00163/艾滋病补充项目8出版物Moudgil T，Mchida CA。 酵母双杂交系统鉴定与之相互作用的分子 猿猴逆转录病毒env基因产物。在第十六届年会的节目中 艾滋病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)。