MOLEC CHAPERONES STRUCT & EXPRESSION IN ACTIVATED HIV T CELLS: HISPANIC

尽管我们对分子生物学的理解取得了迅速的进展， HIV-1的生物学和宿主范围，一些内在细节， HIV-1是如何诱发艾滋病的，至今仍是一个谜。 在努力 提高我们对艾滋病现象的认识， 蛋白质因子的表达功能参与了 HIV-1中人T淋巴细胞生长和增殖的控制 积极的个人，需要更仔细的检查，最近， 可能涉及分子伴侣，一类特殊的 在细胞增殖、生长和增殖中的遗传保守蛋白质， 除了提供热保护外， 其他压力，引起了相当大的兴趣。 比如说， 有迹象表明，几种分子伴侣（如HSP 70 和热休克蛋白90）可能在应激反应和生长中具有功能性作用 人类T淋巴细胞。 因此，据推测， 蛋白质优先在G1中期合成， 细胞周期的一部分，负责细胞的变异性 持续时间和增长率，并占很大比例f 在氮激活的细胞中合成。 事实上，T细胞的激活 在逆转录病毒学中构成了一个非常重要的研究领域， 艾滋病 前病毒活化与T细胞活化密切相关 而且，我们需要更好地了解这一过程， 要求操纵该系统，使艾滋病患者受益。 由于分子伴侣在许多细胞中起着重要作用， 生理过程，可以合理地推测， 这些蛋白质的表达和功能在HIV感染过程中可能会发生改变。 与正常人相比，感染。 的长期目标 本申请旨在揭示分子生物学的机理 有丝分裂原诱导的人T细胞活化过程中的伴侣， 确定艾滋病毒感染后是否会引起这种情况的变化。 将通过以下具体措施实现长期目标 目的：（1）研究分子生物学中基因表达的动力学 分子伴侣，在转录和翻译水平，在 丝裂原诱导的T细胞活化，（2）建立相关性 分子伴侣的基因表达动力学和 T细胞活化所需的其他蛋白质因子，如 细胞因子和原癌基因;（3）分子伴侣的鉴定 那些在结构上表达的，那些被诱导的， 在T细胞活化的不同阶段受到抑制， （4）评价蛋白质的含量 T细胞活化过程中分子伴侣的磷酸化，（5） 确定分子伴侣中的磷酸化位点（S） （6）研究T细胞活化过程中的细胞定位 T细胞中的分子伴侣在不同阶段 通过免疫电子显微镜进行活化。

Despite rapid advances made in our understanding of the Molecular Biology and host range of HIV-1, some of the intrinsive details by which the HIV-1 induces AIDS remain a mystery. In efforts of advancing our knowledge in regards to the AIDS Phenomena, changes in the expression functionality of protein factors involved in the control of growth and proliferation of human T-lymphocytes in HIV-1 positive individuals, require a closer examination, Recently, the possible involvement of Molecular Chaperones, a specialized class of phylogenetically conserved proteins, in cell proliferation, growth and transformation, in addition to providing protection from thermal and other stresses, has attracted considerable interest. For instance, there are indications that several Molecular Chaperones (e.g hsp 70 and hsp 90) may have functional roles in stress responses and growth of human T lymphocytes. Thus, it has been postulated that both proteins are preferentially synthesized in the mid G1 phase, the portion of the cell cycle responsible for the variability in cell duration and growth rate and, account for a significant proportion f synthesis in nitrogen-activated cells. Indeed, activation of T cells constitutes a very important area of study within retrovirology and AIDS. Proviral activation is closely linked with T Cells activation and, we need to gain a better understanding of this process as a requirement to manipulate the system to the benefit of AIDS patients. Since Molecular Chaperones play important roles in numerous cellular physiological processes, it is reasonable to speculate that the expression and function of these proteins may be altered during HIV infection as compared to normal individuals. The long term goal of the present application is to unravel the mechanics of Molecular Chaperones during mitogen-induced human T cells activation and, to determine if changes in that scenario are induced after HIV infection. The long term goal will be approached through the following specific aims: (1) To study the kinetics of gene expression for Molecular chaperones, at the transcriptional and translational levels, during mitogen induced T cell activation, (2) To establish correlations between the kinetics of gene expression for Molecular Chaperones and other protein factors, required for T cell activation, such as cytokines and protooncogenes, (3) To identify the Molecular Chaperones that are consitutively expressed and those which are induced or suppressed at different stages of T cell activation, and to partially characterize them, (4) To evaluate the degree of protein phosphorylation on Molecular Chaperones during T cell activation, (5) To determine the site (S) of phosphorylation in Molecular Chaperones during T cell activation and, (6) To study the ultracellular location of Molecular Chaperones in T cells at different stages during activation by Immunoelectron Microscopy.