INTERACTION OF HIV, MACROPHAGES, AND SALMONELLA

沙门氏菌病是本病患者发病的主要原因。 获得性免疫缺陷综合征(艾滋病)。我们的初选结果是 实验表明，沙门氏菌，而不是几个 其他革兰氏阴性细菌，会导致细菌数量急剧增加 HIV在原代人单核细胞和巨噬细胞中的复制 与病毒潜伏在一起。沙门氏菌的这种作用是由两个 信号，一种分泌的多肽，可诱导肿瘤的产生 坏死因子α(TNFpha)和第二个信号传递 这种细菌不仅能够入侵巨噬细胞， 但也能在宿主细胞内存活。总体目标是 确定沙门氏菌在体内诱导HIV复制的机制 针对感染HIV的巨噬细胞，我们提出了以下具体目标：1) 沙门氏菌对HIV复制的刺激作用 在人外周血单核细胞中；2)克隆了该基因(S) 沙门氏菌衍生的肿瘤坏死因子α诱导物(STI)；3)鉴定 沙门氏菌来源的肿瘤坏死因子α诱导肿瘤坏死因子α的机制 以及4)确定沙门氏菌信号的性质 与肿瘤坏死因子α诱导剂协同行动，促进高水平艾滋病毒 在感染艾滋病毒的U1细胞中产生。这篇文章中概述的研究 应用程序应提供对 巨噬细胞、艾滋病毒和沙门氏菌之间的相互作用导致 增强了病毒的复制。此外，这些结果 这些研究将为今后关于 内化沙门氏菌的信号通路(S) 并触发艾滋病毒的复制。总而言之， 了解沙门氏菌感染对艾滋病毒复制的影响 在巨噬细胞中的作用可能为调节 人类免疫缺陷病毒感染患者的疾病进程 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.