HIV and Female Genital Tract Flora

HIV 和女性生殖道菌群

• 批准号: 8319574
• 负责人: GREGORY T SPEAR
• 金额: $ 26.33万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8319574
• 关键词: Address; Affect; Bacteria; Biological Assay; Biological Response Modifiers; Biometry; CD4 Positive T Lymphocytes; Cell Line; Cells; Cervical; Clinical; Collaborations; Data; Environment; Epidemiology; Estrogens; Female; Gardnerella vaginalis; Genital system; HIV; HIV Infections; Heterosexuals; Human; Immune; Immune response; Immunity; Instruction; Laboratories; Lactobacillus; Lead; Measures; Microscopic; Molecular; Mucous body substance; Mycoplasma hominis; Pathogenesis; Plasma; Population Heterogeneity; Postmenopause; Predisposition; Premenopause; Principal Investigator; RNA; Risk; Role; Running; Rwanda; Sampling; Sampling Studies; Serum; Sexual Transmission; Specimen; Techniques; Time; Tissues; Vaginal Douching; Viral Load result; Virus; Woman; Work; cell type; chemokine; cytokine; genital secretion; high risk; human female; microbial; microbicide; tissue culture; transmission process; vaccine efficacy; virology

Studies by us and others suggest that bacterial flora (microbiota) influences HIV expression in the female genital tract. Our studies show that in HIV-infected women, the amount of HIV in lower genital tract secretions is positively associated with the amount of Mycoplasma hominis, negatively associated with actobacilli, but not associated with Gardnere//a vaginalis. While intriguing, the previous studies only assessed the association of HIV with three of the bacteria types that can be present in genital tract. More than 20 different bacterial species can make up the genital flora in women. Importantly, the combinations of these bacteria that are found in the genital tract are variable. Also, several of the major types of bacteria can not be cultured, or are difficult to culture, and therefore have not been studied in relation to HIV. In aim 1, we will use molecular techniques (real time PCR and pyrosequencing) to identify genital tract bacteria, thus avoiding culture, in order to investigate the relationship between levels of genital tract HIV and the microbiota. In aim 2 we will investigate the hypothesis that the effects of bacterial flora on HIV expression in the female genital tract are not direct, but are associated with and potentially caused by changes in specific mmune molecules; recent studies by us indicate that HIV levels in genital secretions are associated with certain immune mediators. Multiplex luminex assays will be used to assess cytokines, chemokines and nnate immune mediators in genital tract secretions, which will be compared with HIV and bacterial flora data. We also will collaborate with Dr. Hope to detemine the impact of sialidases on the protective activity of mucous. In aim 3, in collaboration with Dr. Lurain of Core C, we will assess the effects of genital secretions on HIV replication in both ex vivo cervical explants and in U1 cells, and determine the identity of the stimulatory activities. Lastly, in aim 4, in associationwith Drs. Novak and Baum of Project III, we will investigate the relationship of genital tract flora with anti-HIV immunity in highly exposed HIV-seronegative women. This project will lead to a better understanding of the factors that affect heterosexual transmission of HIV. This is important since understanding the impact of different bacterial species will allow us to understand how we could manipulate that microbial environment to reduce the risk of transmission or increase the efficacy of vaccines or microbicides. RELEVANCE (See instructions): Each year, millions of people are infected with HIV by sexual transmission. This work will lead to a better understanding of the factors that affect sexual transmission of HIV and could lead to treatments that reduce HIV transmission.

我们和其他人的研究表明，细菌菌群（微生物群）影响女性的HIV表达 生殖道。我们的研究表明，在感染HIV的女性中，下生殖道中的HIV量 分泌物与支原体hominis的数量正相关，与 Actobacilli，但与Gardnere无关//阴道。在吸引人的同时，只有先前的研究 评估了HIV与生殖道中可能存在的三种细菌类型的关联。更多的 超过20种不同的细菌物种可以构成女性的生殖器菌群。重要的是，组合 在生殖道中发现的这些细菌是可变的。此外，几种主要类型的细菌可以 不培养或难以培养，因此尚未与HIV有关。在AIM 1中，我们 将使用分子技术（实时PCR和Pyrosequencing）来鉴定生殖道细菌，从而 避免培养，以研究生殖道艾滋病毒水平与 微生物群。在AIM 2中，我们将研究细菌菌群对HIV表达的影响的假设 女性生殖道不是直接的，而是与特定变化有关的并可能与 mmune分子；我们最近的研究表明，生殖器分泌中的艾滋病毒水平与 某些免疫介质。多重Luminex分析将用于评估细胞因子，趋化因子和 生殖道分泌物中的Nnate免疫介质，将与HIV和细菌菌群进行比较 数据。我们还将与Hope博士合作，以确定唾液酸酶对 粘液。在AIM 3中，与C核C的Lurain博士合作，我们将评估生殖器分泌的影响 在离体宫颈外植体和U1细胞中的HIV复制上，并确定 刺激活动。最后，在AIM 4中，与Drs协会。 III项目的Novak和Baum，我们将 研究生殖道菌群与高度暴露的HIV辅助性抗HIV免疫的关系 女性。该项目将更好地理解影响异性传播的因素 艾滋病病毒。这很重要，因为了解不同细菌物种的影响将使我们能够 了解我们如何操纵微生物环境以降低传播的风险或 提高疫苗或杀菌剂的功效。 相关性（请参阅说明）： 每年，数以百万计的人通过性传播感染了艾滋病毒。这项工作将导致更好 了解影响艾滋病毒性传播的因素，并可能导致降低的治疗 艾滋病毒传播。