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).

猿猴D型逆转录病毒是猿猴获得性 亚洲生物医学研究界的免疫缺陷综合征 猕猴，并可以作为模型系统，在理解的作用， 调节细胞嗜性的包膜糖蛋白基因多样性 和艾滋病发病机制中的作用。 逆转录病毒经历高频率的 它们的env基因发生突变， 导致了新的病理性疾病的出现 变体。 我们已经完成了分子克隆和测序 D型猿猴逆转录病毒（SRV血清组2; D2/RHE/OR）的基因组，和 从地方性感染的恒河猴中回收的变异病毒 感染了典型的血清型2病毒 感染性分子基因组 D2/RHE/OR和一个变异体D2/RHE/OR/V1已被回收。 构建相互嵌合病毒以分析 病毒基因组决定簇对体外 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，特别是 Hut-78和MT-细胞，以及多种病毒基因组决定簇， 影响取向 此外，我们还分离了感染性分子， 血清组4（D4/CYN/CA）和血清组5（D5/RHE/OR）SRVs的克隆。 这些额外的基因组克隆的完整序列分析表明， 血清群4和5的SRVs在遗传上与所有 以前鉴定的血清群。 在最近的工作中，使用 酵母双杂交系统，我们现在正试图 分子克隆编码env相互作用蛋白的基因， 包括潜在的SRV受体和细胞信号分子。 的 血清群2、4和5的SRVs的全序列分析， 提供了关于遗传多样性的重要信息。 猿类逆转录病毒 这些分子克隆和潜在的 鉴定SRV受体和细胞信号分子将 为将来的结构化提供必要的分子试剂 功能和细胞/组织向性实验。 资金 RR 00163/艾滋病补充项目8出版物Moudgil T，町田CA. 酵母双杂交系统鉴定与之相互作用的分子 猴逆转录病毒env基因产物。 在十六年的计划 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）。