The Role of Inflammation and Immune Activation in HIV-1 Infection In Women

炎症和免疫激活在女性 HIV-1 感染中的作用

• 批准号: 8500416
• 负责人: JULIE M. OVERBAUGH
• 金额: $ 20.34万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH 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/8500416
• 关键词: Address; Affect; Bacterial Vaginosis; Biological; Blood; CD4 Positive T Lymphocytes; Case-Control Studies; Cells; Characteristics; Clinical Data; Cohort Studies; Complex; Contraceptive Usage; Data; Disease Progression; Environment; Event; Exposure to; Female; Foundations; Genetic; Genital system; Goals; Grant; HIV; HIV Infections; HIV-1; Hormonal; Hormones; Immune; Immune response; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Instruction; Intervention; Kenya; Lead; Measures; Methods; Monitor; Natural Immunity; Outcome; Phenotype; Plasma; Population; Postpartum Period; Postpartum Women; Predisposition; Pregnancy; Pregnant Women; Prevention; Principal Investigator; Property; Risk; Role; Sampling; Sexually Transmitted Diseases; Supporting Cell; Surrogate Markers; T-Lymphocyte; Testing; Time; Vagina; Viral; Virus; Virus Diseases; Virus Replication; Woman; cofactor; cohort; cytokine; design; genetic variant; high risk; hormonal contraception; immune activation; microbicide; population based; programs; prospective; response; transmission process; Address; Affect; Bacterial Vaginosis; Biological; Blood; CD4 Positive T Lymphocytes; Case-Control Studies; Cells; Characteristics; Clinical Data; Cohort Studies; Complex; Contraceptive Usage; Data; Disease Progression; Environment; Event; Exposure to; Female; Foundations; Genetic; Genital system; Goals; Grant; HIV; HIV Infections; HIV-1; Hormonal; Hormones; Immune; Immune response; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Instruction; Intervention; Kenya; Lead; Measures; Methods; Monitor; Natural Immunity; Outcome; Phenotype; Plasma; Population; Postpartum Period; Postpartum Women; Predisposition; Pregnancy; Pregnant Women; Prevention; Principal Investigator; Property; Risk; Role; Sampling; Sexually Transmitted Diseases; Supporting Cell; Surrogate Markers; T-Lymphocyte; Testing; Time; Vagina; Viral; Virus; Virus Diseases; Virus Replication; Woman; cofactor; cohort; cytokine; design; genetic variant; high risk; hormonal contraception; immune activation; microbicide; population based; programs; prospective; response; transmission process

Multiple biological cofactors have been shown to increase a woman's susceptibility to HIV-1 infection, including sexually transmitted diseases, vaginal flora, hormonal contraceptive use and pregnancy. Many of these factors cause inflammation or immune activation, suggesting a possible mechanism for their affect on HIV-1 susceptibility. The proposed aims of this project will test the hypothesis that innate immune conditions, including immune activation and inflammation, impact HIV-1 susceptibility in women. The foundation for this hypothesis comes from many observations, including the above-mentioned results suggesting that several of the biological cofactors for HIV-1 acquisition alter innate immunity, the fact that immune activation is known to make CD4+T lymphocytes more permissive to infection, and the fact that immune activation early in HIV-1 infection appears to fuel virus replication and disease progression. Although there are several lines of support for this hypothesis, the association between inflammation or immune activation has never been directly examined in relation to risk of HIV-1 acquisition in women. We propose to test this hypothesis by examining cytokine profiles, which provide a surrogate marker of innate immune conditions, just prior to the time of HIV-1 infection, in relation to risk of HIV-1 infection in several populations. The cohorts for these studies will include a 14 year seroincident female cohort in Mombasa, Kenya and a cohort of pregnant women in Nairobi, Kenya. We will take advantage of banked samples and clinical data from the Mombasa cohort as well as samples and data collected as part of Projects 1 and 2 to address the Aims of Project 3. This integration with long-term cohort studies by our group and with the new studies in other Projects will provide considerable opportunities for synergy among projects in the program grant. It will also permit a comprehensive study of innate immune factors at the time of HIV-1 acquisition across multiple high-risk cohorts that will include women with various biological cofactors of importance in determining risk of HIV-1 acquisition in women. RELEVANCE (See instructions): These studies will provide critical data on the characteristics of the innate immune response that impact risk of HIV-infection in women, including women in multiple high-risk groups. In addition, the study is designed to identify a cytokine profile that is associated with increase risk of HIV acquisition in women. This profile may provide a useful surrogate marker for monitoring the impact of new prevention methods, particularly microbicides.

已显示多种生物辅助因子会增加女性对HIV-1感染的敏感性， 包括性传播疾病，阴道菌群，荷尔蒙避孕药使用和怀孕。许多 这些因素会导致炎症或免疫激活，这表明其影响的可能机制 HIV-1敏感性。该项目的拟议目的将检验先天免疫的假设 包括免疫激活和炎症在内的疾病会影响女性HIV-1敏感性。这 该假设的基础来自许多观察结果，包括上述结果 提示一些用于HIV-1采集的生物辅助因子改变了先天免疫，这一事实是 已知免疫激活使CD4+T淋巴细胞更允许感染，并且事实是 HIV-1感染早期的免疫激活似乎为病毒复制和疾病进展提供了促进。 尽管对这一假设有几条支持，但炎症或 从未直接检查过与女性HIV-1获取风险有关的免疫激活。我们 提议通过检查细胞因子谱来检验这一假设，该轮廓提供了先天性的替代标记 在HIV-1感染之前，免疫疾病与几种HIV-1感染的风险有关 人群。这些研究的队列将包括蒙巴萨的14年血清雌性队列 肯尼亚和肯尼亚内罗毕的一群孕妇。我们将利用银行样本和 来自MOMBASA队列的临床数据以及作为项目1和2的一部分收集的样品和数据 解决项目3的目的。与我们小组以及新的长期同队研究的整合 其他项目中的研究将为计划中的项目提供大量协同作用 授予。这还将允许在HIV-1获取时对先天免疫因素进行全面研究 在多个高风险队列中，将包括具有各种重要生物辅助因子的女性 确定女性HIV-1获取的风险。 相关性（请参阅说明）： 这些研究将提供有关先天免疫反应特征的关键数据，以影响风险 女性的HIV感染，包括多个高风险群体的女性。此外，该研究是设计的 确定与女性增加艾滋病毒收购风险有关的细胞因子概况。此个人资料 可能会提供有用的替代标记，以监视新的预防方法的影响，尤其是 微生物。