Role of Exogenous Activation of the Immune System in the Pathogenesis of HIV dis

免疫系统的外源激活在 HIV 发病机制中的作用

• 批准号: 6099018
• 负责人: Mario Ostrowski
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 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/6099018
• 关键词: AIDS; HIV infections; clinical research; helper T lymphocyte; human immunodeficiency virus 1; human subject; human therapy evaluation; human tissue; immunization; leukocyte activation /transformation; leukocyte count; microorganism immunology; monocyte; pathologic process; provirus; receptor expression; serotyping; tetanus toxoid; tissue mosaicism; virus load

This project is directed at delineating the pathogenic mechanisms of HIV infection and the role of immune activation in the propagation of disease and destruction of the immune system. We have demonstrated that, after tetanus toxoid booster inoculation, HIV-1 infected patients had transient increases in plasma viremia after immunization, increases in proviral burden, and increased viral load within lymph nodes. HIV was more easily isolated from PBMCs from the majority of patients after immunization than before immunization. We also demonstrated an enhanced susceptibility of normal PBMCs to HIV infection in vitro after tetanus immunization. Tetanus immunization was associated with dramatic and generally reversible shifts in the composition of plasma viral quasi-species. The plasma viral bursts in most cases reflected a non-specific increase in viral replication, secondary to an expanded pool of susceptible CD4+ T cells. In one patient, however, immunization favored the expansion of M-tropic(NSI) over dual tropic(SI) viruses. In one of three patients the data suggested that immune activation resulted in the appearance in plasma of virus induced from latently infected cells. These findings demonstrate how antigenic stimulation influences the dynamics of HIV replication including the relative expression of different viral variants.

该项目旨在描述病原体 HIV感染的机制和免疫激活的作用 疾病的传播和免疫系统的破坏。 我们已经证明，在破伤风毒素助推器之后 接种，HIV-1感染患者的瞬时增加 免疫后血浆病毒血症，前病毒负担增加和 淋巴结内的病毒载量增加。艾滋病毒更容易 从大多数患者的PBMC中分离出来 免疫比免疫之前。我们还证明了 正常PBMC在体外对HIV感染的敏感性增强 破伤风免疫后。破伤风免疫是相关的 随着戏剧性且通常可逆的变化 等离子体病毒准物种。在大多数情况下，血浆病毒爆发 反映了病毒复制的非特异性增加，其次是 易感CD4+ T细胞的扩展池。在一个患者中， 然而，免疫有利于Mtropic（NSI）的扩展 超过双热带（SI）病毒。在三个患者中，数据 建议免疫激活导致出现 来自潜在感染细胞的病毒的血浆。这些发现 证明抗原刺激如何影响 HIV复制，包括不同病毒的相对表达 变体。