Bacterial vaginosis and HIV in the genital tract

细菌性阴道病和生殖道中的艾滋病毒

• 批准号: 6574783
• 负责人: GREGORY T SPEAR
• 金额: $ 19.72万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6574783
• 关键词: Lactobacillus; Mycoplasma; anaerobic bacteria; antibiotics; bacteria infection mechanism; bacterial vaccines; comorbidity; disease /disorder proneness /risk; female; host organism interaction; human immunodeficiency virus; human middle age (35-64); human subject; human therapy evaluation; microorganism culture; microorganism disease chemotherapy; microorganism interaction; nucleic acid quantitation /detection; pathologic process; patient oriented research; vagina; vaginitis; virus infection mechanism; virus load; virus replication; women's health; young adult human (21-34)

Bacterial vaginosis (BV) is a common condition in women characterized by an overgrowth of a mixture of anaerobic and other bacteria, typically including Gardnerella vaginalis and Mycoplasmas. However, the flora that constitutes BV can be highly variable. Women with BV have a higher incidence of HIV infection suggesting that BV increases susceptibility to HIV infection. One expansion for increased susceptibility is that BV organisms replace lactobacilli that produce virucidal substances. However, it is also possible that BV affects HIV replication in the genital tract by either increasing the susceptibility of cells to HIV infection or by stimulating cells to produce virus. A recent study showed that HIV RNA was detected more frequently in cervicovaginal lavage (CVL) fluid from women with BV showed that HIV RNA was detected more frequently in cervico vaginal lavage (CVL) fluid from women with BV than those without. Previous work by our group showed that some BV-associated organisms (e.g. G vaginalis and M. hominis) stimulated HIV expression by infected cells while others (U. Urealyticum and lactobacilli) did not). We hypothesize that colonization by certain BV-associated bacteria increases genital tract virus load (VL). To test this in aim 1 we will obtain CVL samples from a cross-section of HIV+ women with and without BV. The numbers of four specific bacteria, G. vaginalis, M. hominis, Mobiluncus and Lactobacillus will be determined by PCR and compared with the genital tract VL. In aim 2, women with BV will be treated and the effect on genital tract VL and bacterial will be determined. A significant association between HIV and a specific organism, or reduction due to treatment, would indicate that colonization with that organism influences genital tract VL, provide an explanation for how BV increases susceptibility to HIV infection and point strategies for reducing transmission. Earlier we found that expression of a genital tract factor that induces HIV replication (HIF) was significantly associated with BV. We also hypothesize that treatment of BV will decrease HIF expression and will test this aim in aim 3 to determine a cause and effect relationship between BV and HIF. Finally, in aim 4 the effect of BV, HIF and BV-bacteria on induction of specific genital tract immune responses in vaccinated seronegative women will be determined.

细菌性阴道病（BV）是女性的常见状况，其特征是厌氧和其他细菌的混合物过度生长，通常包括阴道和分枝杆菌。但是，构成BV的菌群可能是高度可变的。 BV妇女的HIV感染发生率更高，这表明BV增加了对HIV感染的敏感性。增强敏感性的一种扩展是，BV生物取代了产生病毒物质的乳酸杆菌。但是，BV也可能通过增加细胞对HIV感染的敏感性或刺激细胞产生病毒的敏感性来影响生殖道中的HIV复制。最近的一项研究表明，来自BV女性的宫颈阴道灌洗液（CVL）液中检测到HIV RNA的频率更高，表明，来自BV女性的cervico阴道灌洗液（CVL）液中检测到HIV RNA的频率更高。我们小组的先前工作表明，某些BV相关的生物（例如G阴道和Hominis）刺激了受感染细胞的HIV表达，而其他生物则没有（U.尿素和乳酸乳杆菌）。我们假设某些BV相关细菌的定植会增加生殖道病毒载荷（VL）。为了在AIM 1中测试这一点，我们将从有或没有BV的HIV+女性的横截面中获得CVL样品。四种特异性细菌的数量，即阴道，hominis，mobiluncus和乳杆菌的数量，将由PCR确定，并与生殖道VL进行比较。在AIM 2中，将处理具有BV的妇女，并确定对生殖道VL和细菌的影响。艾滋病毒与特定生物之间的显着关联，或因治疗而导致的减少，将表明与该生物体的定植会影响生殖道VL，这为BV如何增加对HIV感染的敏感性以及减少传播的点策略提供了解释。早些时候，我们发现诱导HIV复制（HIF）的生殖道因子的表达与BV显着相关。我们还假设BV的处理将降低HIF表达，并将在AIM 3中测试该目标，以确定BV和HIF之间的因果关系。最后，将确定BV，HIF和BV - 细菌对诱导疫苗接种妇女的特定生殖道免疫反应的影响。