INTERACTION OF HIV, MACROPHAGES, AND SALMONELLA

沙门氏菌病是导致糖尿病患者发病的主要原因。 获得性免疫缺陷综合征（艾滋病）。我们最初的结果 实验表明，沙门氏菌，而不是几个 其他革兰氏阴性细菌物种，诱导 HIV在原代人单核细胞和细胞系巨噬细胞中的复制 潜伏在病毒中沙门氏菌的这种作用是由两个 信号，一种诱导肿瘤产生的分泌多肽 坏死因子α（TNF α）和递送的第二信号 细菌不仅能侵入巨噬细胞， 也能在宿主细胞内存活的总体目标是 确定沙门氏菌诱导HIV复制的机制， HIV感染的巨噬细胞，我们提出以下具体目标：1） 表征沙门氏菌对HIV复制的刺激作用 在人外周血单核细胞中; 2）为了克隆用于人外周血单核细胞的基因， 沙门氏菌衍生的TNF α-诱导剂（STI）; 3）为了表征 沙门氏菌衍生的TNF α诱导TNF α的机制 诱导物;和4）确定沙门氏菌信号的性质， 与TNF α诱导剂协同作用，促进高水平的HIV 在HIV感染的U1细胞中生产。本文中概述的研究 应用程序应该提供新的和重要的见解， 巨噬细胞、艾滋病毒和沙门氏菌之间的相互作用， 增强病毒的复制。此外，这些结果 这些研究将为今后的研究奠定坚实的基础， 信号通路（s）通过内化沙门氏菌与 细胞核并触发艾滋病毒复制。总之， 了解沙门氏菌感染对HIV复制的影响 在巨噬细胞中的表达可能为调节 在感染的患者中疾病过程的进展 病毒

Salmonellosis is a major cause of morbidity in patients with the Acquired immune Deficiency Syndrome (AIDS). The results of our initial experiments demonstrate that Salmonella bacteria, as opposed to several other Gram-negative bacterial species, induce a dramatic increase in HIV replication in primary human monocytes and cell line macrophages latently with the virus. This action of Salmonella is mediated by two signals, a secreted polypeptide that induces the production of tumor necrosis factor alpha (TNFalpha) and a second signal that is delivered by bacteria that possess the ability to not only invade the macrophage, but also survive within the host cell. With the overall goal of defining the mechanism by which Salmonella induce HIV replication in HIV-infected macrophages, we propose the following specific aims: 1) To characterize the stimulatory effect of Salmonella on HIV replication in human peripheral blood monocytes; 2) To clone the gene(s) for the Salmonella-derived TNFalpha -inducer (STI); 3) To characterize the mechanism of TNFalpha induction by the Salmonella-derived TNFalpha - inducer; and 4) To determine the nature of the Salmonella signal that acts in concert with the TNFalpha - inducer to promote high level HIV production in HIV-infected U1 cells. The studies outlined in this application should provide new and important insights into the interplay between the macrophage, HIV, and Salmonella that results in enhanced replication of the virus. In addition, the results from these studies will establish a strong foundation for future studies on the signaling pathway(s) by which internalized Salmonella communicate with the cell nucleus and trigger HIV replication. In summary, the understanding of the impact of Salmonella infection on HIV replication in macrophages may provide new insights into the factors that regulate the progression of the disease process in patients infected with the virus.