M FERMENTANS AND THE PROGRESSION OF SIV DISEASE

M FERMENTANS 和 SIV 疾病的进展

• 批准号: 2068157
• 负责人: JERRY K. DAVIS
• 金额: $ 33.82万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2068157
• 关键词: Macaca nemestrina; Mycoplasma; T lymphocyte; cell population study; genetic strain; host organism interaction; human tissue; immunosuppression; leukocyte activation /transformation; microorganism interaction; monocyte; opportunistic infections; pathologic process; serology /serodiagnosis; simian AIDSs; simian immunodeficiency virus; tissue /cell culture; Macaca nemestrina; Mycoplasma; T lymphocyte; cell population study; genetic strain; host organism interaction; human tissue; immunosuppression; leukocyte activation /transformation; microorganism interaction; monocyte; opportunistic infections; pathologic process; serology /serodiagnosis; simian AIDSs; simian immunodeficiency virus; tissue /cell culture

Epidemiological studies indicate that cofactors may be involved in the rate of progression of acquired immunodeficiency disease (AIDS) and certain mycoplasmas, especially Mycoplasma fermentans strain incognitus, have been proposed as cofactors. The mitogenic properties of mycoplasmas could increase HIV production by infected lymphocytes; other mitogens that act on T cells are known to enhance HIV production in vitro. Furthermore, increased virus production is known to be associated with clinical progression of disease in HIV-infected individuals. An animal model will be needed to prove whether or not cofactors are involved, and of the available models, simian immunodeficiency virus (SIV) in macaques is the most similar to HIV infection of humans. Our long term goals are to use the SIV model to determine (i) whether M. fermentans is a cofactor for SIV infection and accelerates development of AIDS-like disease; (ii) whether immunosuppression is required for M. fermentans infection; i.e., M. fermentans is only an opportunistic pathogen; and (iii) the mechanisms by which M. fermentans and SIV interact in either situation. Specific objectives for the current proposal are to: determine which strains of M. fermentans, including isolates from AIDS patients, nonspecifically activate macaque lymphocytes and monocytes and characterize the responding lymphocyte subpopulation(s); determine the effects of these strains of M. fermentans on production of SIV in vitro and correlate this with nonspecific activation; determine if the SIV model is confounded by the presence of M. fermentans or indigenous mycoplasmas; characterize the ability of M. fermentans to infect macaques; use macaques infected with M. fermentans to delineate the natural history of M. fermentans infections, identify the site(s) of organism localization, and optimize cultural and serological assays; determine the effects of M. fermentans infection on SIV infection in vivo and on rate of progression of SIV-induced AIDS-like disease and correlate rate of progression with nonspecific activation of lymphoid cells and virus production. Almost all of the techniques to be used in these studies are established in the laboratories of the PI, CO-PI, or Co-Investigators. The virus to be used in these studies, SIVsmmPBjl4-bcl1 is a biological clone; the sequence of the virus is known, thus primers for the SIV PCR can be easily prepared.

流行病学研究表明，辅助因子可能参与 获得的免疫缺陷疾病（AIDS）和 某些支原体，尤其是支原体发酵肌菌株，隐身， 已提出为辅助因子。 支原体的有丝分裂特性 可能通过感染的淋巴细胞增加HIV的产生；其他有丝分裂剂 已知该作用在T细胞上可以增强体外HIV产生。 此外，已知病毒产生的增加与 艾滋病毒感染者疾病的临床进展。 动物 需要模型来证明是否涉及辅助因子，并且 在可用模型中，猕猴中的猿猴免疫缺陷病毒（SIV） 与人类的艾滋病毒感染最相似。 我们的长期目标是 使用SIV模型来确定（i）Fermentans M. 用于SIV感染并加速艾滋病样疾病的发展； （ii） 是否需要发酵生。 IE。， M. Farmentans只是一种机会性病原体。 （iii）机制 Fermentans和Siv在任何情况下都相互作用。 具体的 当前建议的目标是：确定M的哪些菌株。 发酵犬，包括来自艾滋病患者的分离株，非特定于 激活猕猴淋巴细胞和单核细胞，并表征 反应淋巴细胞亚群；确定这些影响 发酵罐菌株在体外生产SIV并将其关联 非特异性激活；确定SIV模型是否被混淆 发酵芽孢杆菌或土著分枝杆菌的存在；表征 发酵杆菌感染猕猴的能力；使用感染的猕猴 M. Fermentans描绘了发酵罐的自然历史 感染，识别生物本地化的位置并优化 文化和血清学测定；确定发酵乳杆菌的影响 体内感染SIV感染的感染和进展速度 SIV引起的类似艾滋病的疾病以及与进展速率相关的 淋巴样细胞和病毒产生的非特异性激活。 几乎 这些研究中使用的所有技术都是在 PI，Co-Pi或共同研究器的实验室。 要使用的病毒 在这些研究中，SIVSMMPBJL4-BCL1是一种生物克隆。序列 该病毒是已知的，因此很容易制备SIV PCR的引物。