HIV ACTIVATION IN ALCOHOL-AIDED G VAGINALIS VIRULENCE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究旨在探索一种创新的方法，以了解酒精增强的共同感染因子毒力因子在女性艾滋病促进中的作用。这项研究验证了一个新的假设，即阴道加德纳菌是女性主要的机会性HIV合并感染因子;迷走神经炎的特征是一种重要的毒力因子，即唾液酸酶。唾液酸酶是一种从高度唾液酸化的病毒体包膜gp 120和可感染的靶宿主细胞CD 4/趋化因子受体中去除唾液酸的酶，并且在这样做的过程中，显著增强它们的高亲和力相互作用、病毒结合、进入宿主细胞和病毒复制。已知唾液酸化的程度对HIV和其他灵长类慢病毒的复制程度和感染性有相反的影响。唾液酸酶的活性会因酗酒时酒精含量的增加而增强。这一假设的一个推论是，在合并感染G。阴道炎和艾滋病测试了以下子假设：1）加德纳菌唾液酸酶将有效地从gp 120和CD 4中去除唾液酸; 2）酒精增强HIV病毒外壳中的gp 120和CD 4+靶细胞如T淋巴细胞、单核细胞样细胞和外周血单核细胞（PBMC）上的CD 4的这种去唾液酸化的速率和程度; 3）gp 120和CD 4的去唾液酸化促进HIV进入靶细胞并在靶细胞中复制;病毒进入和复制的迷走神经唾液酸酶。我们一直在测试各种唾液酸酶对猕猴细胞系和PBMC中HIV和SIV感染性的影响。一般来说，我们已经发现，感染前的唾液酸酶治疗增加了HIV和SIV在细胞中生长的能力。这种效果在酒精的存在下增加。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This research is to investigate an innovative approach towards understanding the role of alcohol-enhanced co-infective agent virulence factors in AIDS promotion in women. The research tests the novel hypothesis that Gardnerella vaginalis is a major opportunistic HIV co-infection agent for women; G. vaginalis features an important virulence factor, i.e, sialidase. Sialidase is an enzyme that removes sialic acid from highly sialylated virion envelope gp120 and infectable target host cell CD4/chemokine receptors and, in so doing, dramatically escalates their high affinity interaction, virus binding, entry into the host cell, and viral replication. The degree of sialylation is known to inversely affect the extent of replication and the infectivity of HIV and other primate lentiviruses. Sialidase activity is enhanced by alcohol levels that are achieved during binge drinking. A corollary of this hypothesis is that prophylaxis with sialidase inhibitors will reduce the risk of AIDS promotion in alcohol-abusing women co-infected with G. vaginalis and HIV. The following sub-hypotheses tested: 1) Gardnerella sialidase will effectively remove sialic acid from gp120 and CD4; 2) alcohol enhances the rate and extent of this de-sialylation of gp120 in the HIV viral coat and CD4 on CD4+ target cells such as T lymphoid, monocytoid, and peripheral blood mononuclear cells (PBMC); 3) the de-sialylation of gp120 and CD4 promotes HIV entry and replication in the target cell; and 4) that sialidase inhibitors prevent enhancement by G. vaginalis sialidase of viral entry and replication. We have been testing the effects of various sialidase enzymes on the infectivity of both HIV and SIV in cell lines and PBMC from macaques. In general we have found that sialidase treatment prior to infection increases the ability of HIV and SIV to grow in cells. This effect is increased in the presence of alcohol.