Genital HSV-1: An Emerging Disease

单纯疱疹病毒1型（HSV-1）已成为年轻人生殖器疱疹和新生儿疱疹的主要原因。尽管生殖器HSV-1的重要性日益增加，但生殖器HSV-1的自然史尚未被表征。我们缺乏以下方面的知识：1）解剖部位原发感染后病毒脱落的频率; 2）生殖器对HSV-1的持续炎症反应及其增加HIV感染风险的可能性; 3）HSV-1传播的风险因素，包括传播伴侣的口腔和生殖器病毒脱落模式。为了解决这些差距，我们提出：目标1。定义感染第一年内口腔和生殖器HSV-1脱落的自然史。我们假设生殖器脱落率在感染后的第一年内会急剧下降，这可能表明对HSV-1的免疫应答成功。我们将招募100例实验室记录的原发性生殖器HSV-1感染患者，通过30天的口腔和生殖器自拭子研究，在感染后2个月和11个月测量生殖器和口腔HSV-1脱落。目标2.确定HSV-1获得和生殖器脱落是否与生殖道中携带HIV受体的CD 4 T细胞、树突状细胞和CDS T细胞的浸润相关。我们假设，CD 4和CD 8 T细胞将持续在原发性生殖器病变部位数月，炎症的程度将与生殖器脱落率呈正相关。50名受试者将在每次排毒结束时频繁抽血和生殖器活检，以评估生殖道炎症的持续性，通过CD 4和CDS T细胞的浓度进行测量。目标3：确定传播伙伴是否有HSV-1感染在口腔或生殖器部位，或两者兼而有之。我们将招募50名将HSV-1传播给其伴侣生殖器区域的患者，以收集口腔和生殖器拭子，并确定任一部位的高脱落率是否与HSV-1传播给易感伴侣的时间较短相关。总之，这些研究将帮助我们了解生殖器HSV-1感染的传播动力学，并将提供对HSV-1生殖器免疫反应的深入了解，以告知HSV疫苗设计。

Herpes simplex virus type 1 (HSV-1) has emerged as the leading cause of both genital herpes in young adults and neonatal herpes. Despite the increasing importance of genital HSV-1, the natural history of genital HSV-1 has not been characterized. We lack knowledge regarding: 1) frequency of viral shedding after primary infection by anatomic site; 2) persistence of genital inflammatory response to HSV-1 and its potential to increase the risk of HIV acquisition; and 3) risk factors for HSV-1 transmission, including oral and genital viral shedding patterns in the transmitting partner. To address these gaps, we propose: Aim 1. Define the natural history of oral and genital HSV-1 shedding during the first year of infection. We hypothesize that genital shedding rates will decrease dramatically during the first year after infection, possibly indicating development of a successful immune response to HSV-1. We will enroll 100 persons with laboratory documented primary genital HSV-1 infection to measure genital and oral HSV-1 shedding at 2 and 11 months post infection, through 30-day oral and genital self-swabbing studies. Aim 2. Determine whether HSV-1 acquisition and genital shedding are associated with infiltrates of HIV-receptor bearing CD4 T cells, dendritic cells and CDS T cells in the genital tract. We hypothesize that CD4 and CDS T cells will persist at the site of the primary genital lesions for months, and the magnitude of inflammation will be positively associated with genital shedding rate. 50 participants will have frequent blood draws and genital biopsies at the end of each shedding session to assess the persistence of genital tract inflammation, as measured by concentration of CD4 and CDS T cells. Aim 3. Determine whether transmitting partners have HSV-1 infection at the oral or genital site, or both. We will enroll 50 persons who transmitted HSV-1 to their partners genital area to collect oral and genital swabs and determine whether a high rate of shedding at either site is associated with a shorter time to HSV-1 transmission to susceptible partner. Together, these studies will help us understand transmission dynamics of genital HSV-1 infection and will provide insight into the genital immune response to HSV-1 to inform HSV vaccine design.