MECHANISMS OF T4 CELL RESISTANCE TO HIV

T4细胞抵抗HIV的机制

• 批准号: 3810104
• 负责人: MILES W CLOYD
• 金额: --
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3810104
• 关键词: HIV infections; RNA directed DNA polymerase; cellular immunity; family; gene expression; genetic markers; genetic polymorphism; helper T lymphocyte; human immunodeficiency virus 1; human subject; linkage mapping; molecular cloning; molecular pathology; virus classification; virus cytopathogenic effect; virus infection mechanism; virus replication

The goal of this project is to determine the mechanism by which normal T4 lymphocytes from certain individuals are resistance to infection by certain HIV-I isolates. This phenomenon we conclusively demonstrated in a recent study, which showed that T4 lymphocyte resistance was polymorphic among donors of PBLs. Three donors of 12 tested possessed T4 lymphocytes resistant to 1 out of 10 different HIV-1 isolates each (two donors resistant to HIVC and one donor resistant to HIVAC1). Once the mechanism of this resistance is known, we will be able to make judgements concerning the feasibility of exploiting it as a general therapy against HIV. Thus, our aims are to: 1) determine which step(s) in infection/replication of HIV is blocked in T4 lymphocytes from resistant donors, 2) determine the genetic nature of this resistance by following segregation of the resistance phenotype among family members of resistant donors, 3) attempt to identify and/or map that host gene(s) involved by molecular cloning and linkage analysis, and 4) determine the host cell molecules or processes conferring this resistance. The significance of this work relates both to understanding variable disease outcomes of HIV infection in different people and to a potential for a new avenue for rational drug design.

本项目的目标是确定正常T4 来自某些个体的淋巴细胞对某些 HIV-I分离物。 我们在最近的一次实验中得出结论， 研究表明，T4淋巴细胞抗性在 PBL的捐赠者。 12例供者中3例为T4淋巴细胞 对10种不同HIV-1分离株中的1种（两个供体）均具有耐药性 一个供体对HIVAC 1具有抗性）。 一旦机制 这种阻力是已知的，我们将能够作出判断， 将其作为抗艾滋病毒的一般疗法的可行性。 因此，在本发明中， 我们的目标是：1）确定感染/复制中的哪些步骤 HIV在来自耐药供体的T4淋巴细胞中被阻断，2）确定 这种抗性的遗传性质，通过以下分离的 耐药供体家族成员中的耐药表型，3）尝试 鉴定和/或定位分子克隆所涉及宿主基因， 连锁分析，以及4）确定宿主细胞分子或过程 赋予这种抵抗力。 这项工作的意义涉及到两个方面， 了解不同国家艾滋病毒感染的不同疾病结果 人们和潜在的一个新的途径，合理的药物设计。