HSV-2 shedding: role of hormonal contraception and BV

描述(由申请人提供)：本提案描述了一项为期5年的培训计划，旨在培养生殖传染病领域的独立研究人员，特别是女性生殖器疱疹感染。这一奖项将为申请者提供宝贵的教学培训和多学科指导团队的人类和动物研究经验。 单纯疱疹病毒2型(HSV-2)流行传播的一个重要因素是其在生殖道的高频率无症状脱落，因为病毒的传播通常发生在这些亚临床重新激活的时期。因此，迫切需要更好地了解与HSV-2重新激活和脱落相关的风险因素。此外，提高我们对HSV-2重新激活相关的致病机制的理解也很重要。由于全球超过1亿妇女使用激素避孕药，而细菌性阴道病是阴道症状的一种非常常见的原因，即使与HSV-2生殖器脱落有轻微联系，也会导致病毒传播的重大可归因性风险。 因此，本研究将评估： 1.在一项对102名妇女进行的自然史研究中，与不使用激素避孕药的妇女相比，使用激素避孕药(口服避孕药或去甲孕酮)对每日生殖道HSV-2脱落的影响 2.无症状细菌性阴道病对HSV-2每日生殖道脱落频率的影响评估30例细菌性阴道病治疗前后的脱落频率3.外源性类固醇激素对HSV特异性T淋巴细胞抑制HSV在感觉神经元重新激活及随后在上皮表面脱落的作用。

DESCRIPTION (provided by applicant): This proposal describes a 5-year training program for the development of an independent researcher in the area of reproductive infectious diseases, specifically genital herpes infections in women. This award would provide the applicant valuable didactic training and human and animal research experience from a multidisciplinary mentoring team. An important contributor to the epidemic spread of herpes simplex virus type 2 (HSV-2) is its high frequency of asymptomatic shedding in the genital tract, as transmission of the virus usually occurs during these periods of subclinical reactivation. Therefore, an improved understanding of the risk factors associated with HSV-2 reactivation and shedding are urgently needed. In addition, it is important to improve our understanding of the pathomechanisms associated with HSV-2 reactivation. As hormonal contraceptives are used by more than 100 million women worldwide and bacterial vaginosis is a very common cause of vaginal symptoms, even modest associations with genital shedding of HSV-2 would result in substantial attributable risks for transmission of the virus. Therefore, this research will assess: 1. The effects of hormonal contraceptive use, either oral contraceptive pills or depo-medroxyprogesterone, on daily genital tract shedding of HSV-2 compared to women who do not use hormonal contraceptives in a natural history study of 102 women 2. The effects of asymptomatic bacterial vaginosis on the daily genital tract shedding of HSV-2 by evaluating shedding frequency before and after treatment of bacterial vaginosis in 30 women 3. The effects of exogenous sex steroids on the capacity of HSV-specific T lymphocytes to inhibit HSV reactivation in sensory neurons and subsequent shedding on epithelial surfaces in a murine model.