PATHOGENIC PROVIRUS OF SIVMAC

致病性SIVMAC原病毒

• 批准号: 3144105
• 负责人: WILLIAM A. HASELTINE
• 金额: $ 24.93万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3144105
• 关键词: AIDS; HIV infections; Macaca mulatta; bone marrow; gel electrophoresis; immunofluorescence technique; immunoprecipitation; lymph nodes; lymphocyte; macrophage; molecular cloning; nucleic acid sequence; provirus; radioassay; regulatory gene; simian immunodeficiency virus; tissue /cell culture; virus DNA; virus classification; virus cytopathogenic effect; virus genetics; virus protein; virus replication; western blottings

Although several full length proviral DNAs capable of producing infectious Simian Immune Deficiency virus (SIV) have been isolated, none of the virus strains so produced induce a typical SIV related immune deficiency syndrome in monkeys. The goal of this proposal is to produce a cloned SIV provirus that yields virus which initiates infection and induces typical SIV associated immunologic and central nervous system disease in Rhesus monkeys. Approaches to be taken include isolation of proviral DNA from primary lymphocytes and bone marrow cells of Rhesus monkeys in the early stages of disease, and isolation of an SIVmac251 provirus capable of producing all known SIV encoded proteins. The role of nef and vif of SIVmac251 in initiation of infection will also be investigated. Objectives include: 1. Isolation of 20-30 full-length proviral DNAs from lymphocytes and from macrophages of Rhesus monkeys in the early stage of SIV induced disease. Isolation of 20-30 full-length proviral DNAs from a lymph node tissue from the monkey from which SIVmac251 was originally isolated. Creation of an infectious "consensus" SlVmac251 provirus. 2. Test of the ability of the provirus to produce virus capable of infecting primary cultures of Rhesus lymphocytes and bone marrow macrophages. 3. Test of the ability of three lymphocyte isolates, three bone marrow isolates, one lymph node isolate, and one "consensus" virus isolate to infect and to induce typical SIV disease in Rhesus monkeys. 4. Investigation of difference in the initial growth rate, state of chronic viremia and level of anti-SIV antibodies of viruses isogeneic except for nef and vif. This proposal combines the skills of Dr. William Haseltine, a molecular biologist and virologist, with those of Dr. Norman Letvin, an immunologist and specialist in SIV disease.

虽然几个全长病毒DNA能够产生感染性 已经孤立了猿猴免疫缺陷病毒（SIV），没有病毒 如此产生的菌株会诱导典型的SIV相关免疫缺陷综合征 在猴子。 该提案的目的是生产一个克隆的SIV Provirus 产生引发感染并诱导典型SIV的病毒 恒河猴中相关的免疫和中枢神经系统疾病 猴子。 要采取的方法包括隔离病毒DNA 早期恒河猴的原发性淋巴细胞和骨髓细胞 疾病的阶段，以及能够隔离SIVMAC251病毒 产生所有已知的SIV编码蛋白。 Nef和Vif的作用 SIVMAC251在感染开始时也将进行研究。 目标包括： 1。从淋巴细胞中分离20-30个全长病毒DNA SIV诱导疾病的早期，恒河猴的巨噬细胞。 从淋巴结组织中分离20-30个全长病毒DNA SIVMAC251最初是孤立的猴子。 创建一个 传染性“共识” SLVMAC251病毒。 2。测试病毒生成能力的病毒能力的能力 感染恒河-淋巴细胞和骨髓的原发性培养物 巨噬细胞。 3。测试三个淋巴细胞分离株的能力，三个骨髓 分离株，一个淋巴结分离株，一个“共识”病毒分离到 在恒河猴中感染并诱导典型的SIV疾病。 4。调查初始增长率的差异，慢性状态 病毒抗体的病毒血症和抗体抗体，除非 nef和vif。 该建议结合了威廉·哈塞尔丁博士的技能，这是一个分子 生物学家和病毒学家，与免疫学家诺曼·莱文（Norman Letvin）博士的生物学家 和SIV疾病专家。