HSV-2 shedding: role of hormonal contraception and BV

HSV-2 脱落：激素避孕和 BV 的作用

• 批准号: 6908373
• 负责人: Thomas L. Cherpes
• 金额: $ 12.63万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6908373
• 关键词: clinical research; communicable disease transmission; contraceptives; disease /disorder proneness /risk; disease carrier state; disease reservoirs; female; herpes simplex virus 2; human subject; laboratory mouse; latent virus infection; medroxyprogesterone; oral contraceptives; patient oriented research; reproductive system infection; sex hormones; sexually transmitted diseases; slow release drug; vagina disorder

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.

描述（由申请人提供）：该提案描述了一个为期 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。该奖项将为申请人提供来自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) 流行的一个重要因素是其在生殖道中高频率的无症状传播，因为病毒的传播通常发生在这些亚临床重新激活期间。因此，迫切需要更好地了解与 HSV-2 重新激活和脱落相关的危险因素。此外，提高我们对 HSV-2 重新激活相关病理机制的理解也很重要。由于全世界有超过 1 亿女性使用激素避孕药，而细菌性阴道病是阴道症状的一个非常常见的原因，因此即使与生殖器 HSV-2 脱落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. 在一项针对 102 名女性的自然史研究中，与不使用激素避孕药的女性相比，使用激素避孕药（口服避孕药或去甲羟孕酮）对每日生殖道 HSV-2 脱落的影响 2. 通过评估 30 名女性细菌性阴道病治疗前后的脱落频率，了解无症状细菌性阴道病对每日生殖道 HSV-2 脱落的影响 3. 外源性类固醇对 HSV 特异性 T 淋巴细胞清除病毒能力的影响在小鼠模型中抑制感觉神经元中 HSV 的再激活以及随后在上皮表面的脱落。