HUMAN IMMUNE CELL REGULATED SUPPRESSION OF HIV1

大多数HIV-I感染是由M嗜性毒株引起的， 随后转为主要的T嗜性HIV感染， 艾滋病的快速发展。 更好地理解生物学 HIV感染从M嗜性转变为T嗜性的基础是 在我们控制病毒感染的能力方面， 渐近状态 我们希望验证一个假设， 病毒复制水平的降低将限制从M嗜性 T嗜性HIV-1感染。我们建议阻止早期阶段， 病毒抗原的合成），HIV-1感染， 最近发现的HIV-1基因细胞抑制剂的特性 反式激活 这是重要的，因为目前可用的免疫 治疗或抗病毒剂主要靶向受感染的细胞， 展示病毒抗原。 尽管抗病毒三联疗法取得了进展， 药物治疗，病毒库持续存在于淋巴结中， 不受现有药物的影响（2-5，7，8，15）。 我们建议 早期病毒生命周期的内源性抑制剂将补充 现有的抗病毒治疗达到稳定治愈 艾滋病重要的是，该提案与PA-98-040的目标有关， 由于内源性HIV-1抑制剂的抑制特性， NF 90是由促有丝分裂信号转导途径调节的， 人类初级免疫细胞 更好地理解细胞周期， 人类原代T细胞中HIV-I表达的调节控制将是 重要是设计稳定的艾滋病治疗方法。 这个项目的总体目标是 项目是建立在我们的初步研究和利用 靶向CCR 5表达细胞的免疫脂质体， 表达构建体，以评估其作为抑制剂的有效性， 原代人淋巴细胞中的HIV-I复制。

Most HIV-I infections are initiated by M-tropic strains which subsequently switch to predominantly T-tropic HIV infection during the rapid progression of AIDS. A better understanding of the biological basis of the switch from M-tropic to T-tropic HIV-infection will be significant in our ability to contain viral infection, early in its asymptotic state. We wish to test the hypothesis that a markedly reduced level of viral replication will limit the switch from M-tropic to T-tropic HIV-1 infection. We propose to block early stages, (prior to the synthesis of viral antigens), of HIV-1 infection by exploiting the properties of a recently discovered cellular inhibitor of HIV-1 gene trans-activation. This is significant since currently available immune therapies or the antiviral agents mainly target infected cells which display viral antigens. In spite of the progress in antiviral triple drug therapy, reservoirs of virus persist in lymph nodes that remain unaffected by currently available drugs (2-5, 7, 8, 15). We suggest that an endogenous inhibitor of early viral life cycle will complement the potency of available antiviral therapy to achieve a stable cure for AIDS. Importantly, the proposal is relevant to the goals of PA-98-040, since the inhibitory properties of the endogenous HIV-1 suppressor, NF90, is regulated by the mitogenic signal transduction pathways of human primary immune cells. A better understanding of the cell cycle, regulated control of HIV-I expression in human primary T-cells will be important to design stable cure for AIDS. The overall goal of this project is to build upon our preliminary studies and utilizing immunoliposomes targeted to CCR5 expressing cells, deliver the NF90 expression constructs to assess its effectiveness as an inhibitor of HIV-I replication in primary human lymphocytes.