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Deciphering the impact of sex in early subtype C HIV infection and during HART

Deciphering the impact of sex in early subtype C HIV infection and during HART
解读性别对早期 C 亚型 HIV 感染和 HART 期间的影响
批准号:
10552412
负责人:
Eric Hunter
金额:
$86.43万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
未结题
起止时间:
2022-07-11 至 2027-06-30

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中文摘要
翻译
目前的估计数表明,有1 780万妇女感染了艾滋病毒-1,这是造成艾滋病的主要原因。 育龄妇女死亡。然而,迄今为止,许多关于HIV-1传播和发病机制的研究 关注于单一性别,因此无法直接比较不同性别之间的病程和结果。 男人和女人在这项授权中概述的初步实验利用了来自一组C亚型HIV-1的样本 急性感染的赞比亚男性和女性,允许直接比较病毒,转录和 具有共同遗传背景的个体中两性之间的免疫学特征。 奇怪的是,即使来自急性感染妇女的CD4 + T细胞明显更高活化, (CD38+)与男性相比,女性的病毒载量始终低于男性,无论是在早期阶段, 感染的慢性阶段。另一方面,虽然女性表现出类似的病毒抑制有效水平, 在接受抗逆转录病毒治疗(哈特)的妇女中,她们确实比男子承受着更大的非艾滋病合并症负担。这些 观察结果可能是多种病毒、激素和免疫学之间复杂的相互作用的结果 因素,包括妇女I型干扰素(IFN)的产生增加, 引起免疫激活以及限制病毒复制。为了了解 针对这些性别差异,我们提出三个具体目标: 目的1:评估性别特异性CD4 + T细胞免疫和转录谱的差异, 早期感染 目的2:在ART抑制的女性和男性中,定义免疫细胞激活的景观, 的潜在水库,其潜在的重新激活的存在和不存在性激素。 目的3:明确性激素调节病毒复制的细胞来源和机制。 拟议的实验将填补我们对潜在机制的理解中的一个重大空白 观察到男性和女性之间HIV-1病程和合并症的差异,这是一个重要的 当性别差异在各种疾病中明确定义不同的疾病结局时, 设置.
英文摘要
Current estimates suggest that 17.8 million women are infected with HIV-1 and that it is the leading cause of death in women of reproductive age. However, many studies of HIV-1 transmission and pathogenesis to date have focused on a single sex and are thus unable to directly compare disease course and outcomes between men and women. The initial experiments outlined in this grant utilize samples from a cohort of subtype C HIV-1 acutely infected Zambian men and women that allow for direct comparison of viral, transcriptional and immunologic characteristics between the sexes in individuals with a common genetic background. Paradoxically, even though CD4+ T cells from acutely infected women are significantly more highly activated (CD38+) than in men, women have consistently lower viral load than men, both in the earliest stages and chronic phase of infection. On the other hand, while women exhibit similarly effective levels of viral suppression on antiretroviral treatment (HART), they do bear a greater burden of non-AIDS comorbidities than men. These observations likely result from a complex interaction between a number of viral, hormonal and immunological factors, including the increased production of type I interferons (IFN) in women which can simultaneously cause immune activation as well as restriction of viral replication. In order to understand the molecular basis of these sex-based differences, we propose three Specific Aims: Aim 1: Assess sex-specific differences in immunological and transcriptional profiles of CD4+ T cells in early infection. Aim 2: In ART-suppressed women and men, define the landscape of immune cell activation, the nature of the latent reservoir, and its potential for reactivation in the presence and absence of sex hormones. Aim 3: Define the mechanism and cell source of sex hormone modulation of viral replication in vitro. The proposed experiments will fill a significant gap in our understanding of the mechanisms underlying observed differences in HIV-1 disease course and comorbidities between men and women, an important question at a time when sex differences are clearly defining distinct disease outcomes in various disease settings.
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Deciphering the impact of sex in early subtype C HIV infection and during HART
  • 批准号:
    10663367
  • 项目类别:
  • 资助金额:
    $84.88万
  • 财政年份:
    2022
  • 负责人:
    Eric Hunter
  • 依托单位:
HIV Research for Prevention Conference combining AIDS Vaccine & Microbicides
  • 批准号:
    8731587
  • 项目类别:
  • 资助金额:
    $100.0万
  • 财政年份:
    2014
  • 负责人:
    Eric Hunter
  • 依托单位:
Administrative
  • 批准号:
    8516872
  • 项目类别:
  • 资助金额:
    $44.63万
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    2013
  • 负责人:
    Eric Hunter
  • 依托单位:
PET CONTRAST AGENT FOR INTERROGATING IMMUNODEFICIENCY VIRUS INFECTIONS
  • 批准号:
    8357519
  • 项目类别:
  • 资助金额:
    $7.43万
  • 财政年份:
    2011
  • 负责人:
    Eric Hunter
  • 依托单位:
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