M FERMENTANS AND THE PROGRESSION OF HIV INFECTION

M FERMENTANS 和 HIV 感染的进展

• 批准号: 3148308
• 负责人: GAIL H. CASSELL
• 金额: $ 18.95万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 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/3148308
• 关键词: AIDS; HIV infections; Mycoplasma; T lymphocyte; chronic renal failure; disseminated intravascular coagulation; host organism interaction; human immunodeficiency virus; human tissue; immunosuppression; microorganism interaction; monocyte; opportunistic infections; pathologic process; polymerase chain reaction; virus replication

Within the past 24 months, Mycoplasma fermentans, strain incognitus, has been detected in tissues taken at autopsies from AIDS patients with respiratory, central nervous system (CNS), and renal disease. At the 1991 general meeting of the American Society for Microbiology, increased incidence of M. fermentans was shown in the urine of AIDS patients compared to age and sex-matched non-AIDS patients. In addition, M. fermentans and other mycoplasmas have been reported in the blood of AIDS patients. More recently mycoplasmas, especially M. fermentans strain incognitus, have even been proposed to be cofactors for HIV infection. In fact regulatory mechanisms of replication of human immunodeficiency virus (HIV) in vitro do suggest molecular mechanisms by which mycoplasmas could increase virus production in infected individuals. The mitogenic properties of mycoplasmas could increase HIV production in infected lymphocytes. Indeed other mitogens that act on T cells are known to enhance HIV production in vitro. Increased virus production is known to be associated with clinical progression in HIV-infected individuals. However, the incidence, natural history, pathogenic potential, and clinical significance of M.fermentans in AIDS patients is unknown. In addition, previous epidemiologic investigations have not yet demonstrated any clear association between progression of ADDS and any putative cofactor. Our long term goals are to determine if M. fermentans is either a cofactor in HIV infection or an important opportunistic pathogen. If M.fermentans is either, it then becomes important to determine the natural history of the infection. The specific aims of the present application are to: (i) identify sites of M.fermentans localization in autopsy tissues of AIDS patients and other patients with immunosuppression or other chronic debilitating diseases; (ii) identify HIV infected individuals who are co-infected with M. fermentans and identify matched controls who are HIV positive, M. fermentans negative; and (iii) determine if the rate of change in various parameters, including increase in HIV replication, decline in CD4+ lymphocytes or alterations in other lymphocyte subpopulations, and loss of immune responsiveness is greater in HIV-infected individuals with M. fermentans infection as compared to HIV-infected non-M.fermentans infected matched controls.

在过去 24 个月内，发酵支原体（菌株 incognitus） 在艾滋病患者尸检的组织中检测到 呼吸系统、中枢神经系统（CNS）和肾脏疾病。 在 1991年美国微生物学会全体会议，增加 艾滋病患者尿液中显示发酵支原体的发生率 与年龄和性别匹配的非艾滋病患者进行比较。 此外，M. 据报道，艾滋病患者的血液中存在发酵菌和其他支原体 患者。 最近的支原体，尤其是发酵支原体菌株 incognitus 甚至被认为是 HIV 感染的辅助因子。 事实上，人类免疫缺陷复制的调节机制 体外病毒（HIV）确实表明了支原体的分子机制 可以增加受感染个体的病毒产量。有丝分裂 支原体的特性可能会增加感染者体内艾滋病毒的产生 淋巴细胞。 事实上，已知其他作用于 T 细胞的有丝分裂原 增强HIV在体外的产生。 已知病毒产量增加 与 HIV 感染者的临床进展相关。 然而，发病率、自然史、致病潜力和 M.fermentans 在艾滋病患者中的临床意义尚不清楚。 在 此外，此前的流行病学调查尚未证明 ADDS 的进展与任何假定的之间存在任何明确的关联 辅因子。 我们的长期目标是确定发酵分枝杆菌是否 要么是 HIV 感染的辅助因子，要么是重要的机会因素 病原。 如果 M.fermentans 是其中之一，那么重要的是 确定感染的自然史。 该计划的具体目标 本申请的目的是：（i）鉴定发酵分枝杆菌的位点 艾滋病患者和其他患有艾滋病的患者的尸检组织中的定位 免疫抑制或其他慢性衰弱性疾病； (二) 确定 与发酵支原体共同感染的 HIV 感染者和 确定 HIV 阳性、发酵支原体阴性的匹配对照； (iii) 确定各种参数的变化率， 包括 HIV 复制增加、CD4+ 淋巴细胞减少或 其他淋巴细胞亚群的改变以及免疫能力的丧失 HIV 感染者对发酵支原体的反应性更高 感染与 HIV 感染的非 M.fermentans 感染相匹配 控制。