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

该项目旨在描述致病性 HIV感染的机制和免疫激活在 疾病的传播和免疫系统的破坏 我们已经证明，在破伤风类毒素加强剂后， 接种后，HIV-1感染者的 免疫后血浆病毒血症，前病毒负荷增加，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， 免疫前比免疫后好。我们还展示了一个 正常人外周血单个核细胞对HIV感染的易感性增强 破伤风免疫后。破伤风免疫与 在组成上发生了戏剧性的和通常可逆的变化， 血浆病毒准种。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，继发于 扩增的易感CD 4 + T细胞库。在一个病人身上， 而免疫则有利于M嗜性（NSI）的扩增， 双嗜性（SI）病毒。在三名患者中， 表明免疫激活导致了 从潜伏感染的细胞中诱导病毒血浆。这些发现 展示抗原刺激如何影响 HIV复制包括不同病毒的相对表达 变体。

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.