HSV-2 shedding: role of hormonal contraception and BV

描述（由申请人提供）：本提案描述了一个为期5年的培训计划，用于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。该奖项将为申请人提供多学科指导团队的宝贵教学培训以及人类和动物研究经验。 2型单纯疱疹病毒（HSV-2）流行性传播的一个重要因素是其在生殖道中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再活化期间。因此，迫切需要进一步了解与HSV-2再激活和脱落相关的风险因素。此外，重要的是提高我们对与HSV-2再激活相关的病理机制的理解。由于全世界有1亿多妇女使用激素避孕药，细菌性阴道病是阴道症状的一个非常常见的原因，即使与生殖器排出HSV-2的轻微关联也会导致病毒传播的重大风险。 因此，本研究将评估： 1.在一项102名妇女的自然史研究中，与不使用激素避孕药的妇女相比，使用激素避孕药（口服避孕药或甲羟孕酮）对每日生殖道HSV-2脱落的影响 2.通过对30例无症状性细菌性阴道病患者治疗前后HSV-2的日排出频率进行评价，探讨其对生殖道HSV-2日排出的影响。外源性类固醇对HSV特异性T淋巴细胞抑制感觉神经元中HSV再激活和随后在小鼠模型上皮表面脱落的能力的影响。

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.