ROLE OF INTERFERON-ALPHA IN AIDS PATHOGENESIS

干扰素-α 在艾滋病发病机制中的作用

• 批准号: 3140777
• 负责人: PATRICIA FITZGERALD-BOCARSLY
• 金额: $ 15.88万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-06-15 至 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3140777
• 关键词: AIDS; MHC class II antigen; density gradient ultracentrifugation; fibroblasts; gene expression; genetic transcription; helper T lymphocyte; human immunodeficiency virus 1; human subject; human tissue; immunocytochemistry; immunoelectron microscopy; in situ hybridization; interferons; laboratory mouse; mixed lymphocyte reaction test; monoclonal antibody; opportunistic infections; pathologic process; polymerase chain reaction; protein biosynthesis; tissue /cell culture

The Acquired Immune Deficiency Syndrome (AIDS) results from infection with the human immunodeficiency virus (HIV-1). AIDS is characterized by profound and/or neoplasms in the infected individual. In addition to deficiencies in T mononuclear cells from AIDS patients to make interferon- alpha in response to herpes simplex virus type-1 infected fibroblasts has been observed. This deficiency was strongly correlated with the presence of OI in the patients studied and was also predictive of OI in the follow- up period for those not yet meeting the AIDS case definition. The cells responsible for IFN-alpha production were found to be light density HLA-DR positive cells and shared the phenotype of peripheral blood dendritic cells. In the present application, studies will be undertaken to positively identify the IFN-alpha producing cells, determine the interaction of HIV with this population and determine the mechanism of deficient IFN-alpha production in patients with AIDS and OI. Because the DR-positive cells represent only a small fraction of the mononuclear cells, density gradient techniques and sequential depletions with monoclonal antibodies will be utilized for enrichment. Frequency of IFN-producing cells will be monitored by immunoplaque assay and IFN-gene expression in activated cells will be measured by S1 mapping. Immunocytochemical and immuno-gold techniques for electron microscopy using antibodies to IFN will allow for direct detection of morphology of IFN-alpha producing cells. Enriched IFN-alpha producing cells will be used to determine the effect of HIV on these populations. Whether HIV replicates in and/or kills these cells will be determined and the effect of HIV on functional assays will be investigated. Finally, an evaluation of the mechanism of deficiency of IFN-alpha production in AIDS patients will be undertaken. IFN-alpha producing cells from AIDS patients will be evaluated using techniques developed in this application and functional studies involving co-culture to look for possible suppressor cells or factors will be performed. Together, the proposed experiments involving both basic biology and patient studies should provide important information regarding an important mechanism of AIDS pathogenesis.

获得的免疫缺陷综合征（AIDS）是由感染引起的 人类免疫缺陷病毒（HIV-1）。 艾滋病的特征是 感染者的深刻和/或肿瘤。 此外 来自艾滋病患者的T单核细胞的缺陷以使干扰素 - α响应于单纯疱疹病毒1型感染的成纤维细胞具有 被观察到。 这种缺乏与存在密切相关 在研究的患者中，OI的OI也可以预测随后的OI 尚未满足艾滋病案件定义的人的期限。 细胞 发现负责IFN-α产生的是光密度HLA-DR 阳性细胞并共享外周血树突状的表型 细胞。 在本申请中，将进行研究 积极地识别产生IFN-α的细胞，确定 HIV与该人群的相互作用，并确定 艾滋病和OI患者的IFN-α产生不足。 因为 DR阳性细胞仅代表一小部分单核细胞， 密度梯度技术和单克隆的顺序耗竭 抗体将用于富集。 产生IFN的频率 细胞将通过免疫晶格测定和IFN-GENE表达来监测细胞 活化的细胞将通过S1映射测量。 免疫细胞化学和 使用与IFN抗体的电子显微镜的免疫金技术 允许直接检测IFN-α产生细胞的形态。 富集的IFN-α产生细胞将用于确定 这些人群的艾滋病毒。 艾滋病毒是否复制和/或杀死这些 将确定细胞，HIV对功能测定的影响将是 调查。 最后，评估不足机制 将进行艾滋病患者的IFN-α产生。 IFN-Alpha 将使用技术评估来自艾滋病患者的细胞 在此应用程序和涉及共文化的功能研究中开发 寻找可能的抑制细胞或因素。 一起，提出的涉及基本生物学和患者的实验 研究应提供有关重要的重要信息 AIDS发病机理的机理。