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的重要性与日俱增，但生殖器HSV-1的自然历史尚未被描述。我们缺乏以下方面的知识：1)通过解剖部位初次感染后病毒脱落的频率；2)生殖器对HSV-1的炎症反应的持续性及其增加艾滋病毒感染风险的可能性；以及3)HSV-1传播的危险因素，包括传播伙伴的口腔和生殖器病毒脱落模式。为了解决这些差距，我们建议：目标1。确定感染第一年口腔和生殖器HSV-1脱落的自然历史。我们假设生殖器脱落率在感染后的第一年将显著下降，这可能表明对HSV-1的成功免疫反应的发展。我们将招募100名实验室记录的原始生殖器HSV-1感染者，通过30天的口腔和生殖器自拭子研究，测量感染后2个月和11个月的生殖器和口腔HSV-1脱落情况。目的2.确定HSV-1感染和生殖器脱落是否与生殖道中携带HIV受体的CD4T细胞、树突状细胞和CDS T细胞的浸润有关。我们假设CD4和CDS T细胞将在原发生殖器病变部位持续数月，炎症的程度将与生殖器脱落率呈正相关。50名参与者将在每次脱毛结束时进行频繁的抽血和生殖器活检，以评估生殖道炎症的持久性，以CD4和CDS T细胞的浓度来衡量。目的3.确定传播者是否在口腔或生殖器部位感染HSV-1，或两者都感染。我们将招募50名将HSV-1传播到其伴侣生殖器区域的人来收集口腔和生殖器拭子，并确定其中一个部位的高脱落率是否与HSV-1传播到易感伴侣的时间较短有关。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，并将为HSV-1的生殖器免疫反应提供洞察，为HSV疫苗的设计提供信息。

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.