M FERMENTANS AND THE PROGRESSION OF HIV INFECTION

在过去的24个月里，发酵支原体，一种未知的菌株， 在艾滋病患者的尸检组织中发现， 呼吸系统、中枢神经系统（CNS）和肾脏疾病。 在 1991年美国微生物学会大会，增加了 发病率M.艾滋病患者尿中检出发酵素 与年龄和性别匹配的非艾滋病患者相比。 此外，M. 据报道，艾滋病患者的血液中含有发酵菌和其他支原体 患者 最近，支原体，特别是M.发酵菌株 甚至被认为是HIV感染的辅助因子。 事实上，人类免疫缺陷病毒复制的调节机制 体外研究表明，支原体感染艾滋病毒的分子机制， 会增加感染者体内的病毒产量促有丝分裂 支原体的特性可能会增加感染者的HIV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 增强体外HIV的产生。 已知病毒产量的增加 与HIV感染者的临床进展相关。 然而，发病率，自然史，致病潜力， 发酵支原体在AIDS患者中的临床意义尚不清楚。 在 此外，以前的流行病学调查尚未证明， ADDS进展与任何假定的 辅因子 我们的长期目标是确定M。费门坦斯群岛 要么是艾滋病毒感染的辅助因素，要么是一个重要的机会性因素， 病原体 如果发酵支原体是其中之一，那么重要的是 确定感染的自然史。 的具体目标 （i）鉴定发酵支原体的位点 在艾滋病患者和其他患有 免疫抑制或其他慢性衰弱性疾病;（ii）鉴定 同时感染M.发酵剂和 确定匹配的HIV阳性对照，M.发酵菌阴性; 以及（iii）确定各种参数的变化率， 包括HIV复制增加、CD 4+淋巴细胞减少或 其他淋巴细胞亚群的改变和免疫功能的丧失 在HIV感染者中，M. fermentans 感染与HIV感染的非发酵支原体感染相匹配 对照

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.