INTERFERON ALPHA AND HIV PATHOGENESIS

干扰素α和艾滋病毒发病机制

• 批准号: 6170000
• 负责人: PATRICIA FITZGERALD-BOCARSLY
• 金额: $ 31.53万
• 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 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6170000
• 关键词: CD antigens; HIV infections; antireceptor antibody; carbohydrate receptor; cell differentiation; clinical research; colony stimulating factor; cytokine receptors; dendritic cells; helper T lymphocyte; human immunodeficiency virus 1; human subject; interferon alpha; interleukin 3; leukocyte activation /transformation; mannose; pathologic process; protein biosynthesis

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.

获得性免疫缺陷综合征（艾滋病）是由感染 人类免疫缺陷病毒（HIV-1）。 艾滋病的特点是 感染个体中的深部和/或肿瘤。 除了 艾滋病患者的T单核细胞缺乏产生干扰素- α对单纯疱疹病毒1型感染的成纤维细胞的反应， 被观察到。 这种缺陷与存在密切相关 在研究的患者中的OI，也预测了以下的OI- 对于那些还没有达到艾滋病病例定义的人， 细胞 负责IFN-α产生的是低密度HLA-DR 阳性细胞，具有外周血树突状细胞表型 细胞 在本申请中，将进行研究以 阳性鉴定IFN-α产生细胞，确定 艾滋病毒与该人群的相互作用，并确定 艾滋病和OI患者IFN-α产生不足。 因为 DR阳性细胞仅代表单核细胞的一小部分， 密度梯度技术和单克隆抗体的连续耗竭 抗体将用于富集。 IFN产生频率 将通过免疫空斑测定和IFN-基因表达监测细胞， 将通过S1映射测量活化的细胞。 免疫细胞化学和 使用IFN抗体的电子显微镜免疫金技术将 允许直接检测IFN-α产生细胞的形态。 将使用富集的IFN-α产生细胞来确定 艾滋病在这些人群中 艾滋病毒是否在这些细胞中复制和/或杀死这些细胞 细胞将被确定，HIV对功能测定的影响将被确定。 研究了 最后，对我国农业产业结构调整的不足机制进行了评价。 将在艾滋病患者中进行IFN-α的生产。 IFN-alpha 从艾滋病患者身上生产细胞将使用技术进行评估， 在本申请中开发的和涉及共培养的功能研究 寻找可能的抑制细胞或因子。 总之，所提议的实验涉及基础生物学和病人 研究应提供关于重要的 艾滋病发病机制。