Genital HSV-1: An Emerging Disease

生殖器 HSV-1：一种新出现的疾病

基本信息

批准号：
9307675
负责人：
CHRISTINE MICHELLE JOHNSTON
金额：
$ 17.94万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9307675
关键词：
Accounting Address Affect American Anatomy Antigens Area Biopsy Blood CCR5 gene CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes Childhood Clinical Clinical Trials Collaborations Congenital herpes simplex Counseling Data Dendritic Cells Development Disease Enrollment Epidemiology Exposure to Frequencies Genital system Guidelines HIV HIV Receptors HIV-1 Health Personnel Herpes Simplex Virus Vaccines Herpesvirus 1 Herpetic Stomatitis Human Herpesvirus 2 Immune response Immunity Immunology Infection Inflammation Inflammatory Response Instruction Kinetics Knowledge Laboratories Lesion Measures Memory Methods Mucous Membrane Natural History Neonatal Oral Participant Pathogenesis Patients Pattern Persons Prevention strategy Primary Infection Prospective Studies Publishing Recruitment Activity Recurrence Risk Risk Factors Sexual Partners Sexually Transmitted Diseases Simplexvirus Site Source Swab T-Lymphocyte Time Tissues United States Vaccine Design Virus Virus Shedding Work Youth clinical epidemiology co-infection cohort density evidence base genital herpes genital infection insight neonate oral infection peripheral blood receptor reproductive tract response sexual debut sexual relationship transmission process vaccine candidate young adult

项目摘要

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.

单纯疱疹病毒1型（HSV-1）已成为年轻人和新生儿疱疹生殖器疱疹的主要原因。尽管生殖器HSV-1的重要性越来越重要，但生殖器HSV-1的自然历史尚未得到表征。我们缺乏有关以下方面的知识：1）解剖部位原发感染后病毒脱落的频率； 2）生殖器炎症反应对HSV-1的持久性及其增加艾滋病毒获取风险的潜力； 3）HSV-1传播的危险因素，包括传输伙伴中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。在感染的第一年，定义了口腔和生殖器HSV-1脱落的自然历史。我们假设在感染后的第一年，生殖器脱落率将大大降低，这可能表明对HSV-1产生了成功的免疫反应。我们将招募100人进行实验室记录的原发生殖器HSV-1感染，以测量感染后2和11个月的生殖器和口服HSV-1脱落，直到30天的口服和生殖器自我削减研究。 AIM 2。确定HSV-1采集和生殖器脱落是否与生殖道中的HIV受体CD4 T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细胞将持续在原发性生殖器病变的部位数月，并且炎症的幅度将与生殖器脱落率呈正相关。通过CD4和CDS T细胞的浓度测量，在每个脱落会议结束时，将有50名参与者在每个脱落会议结束时进行频繁的血液抽水和生殖器活检，以评估生殖道炎症的持续性。目标3。确定传播伴侣在口腔或生殖器部位还是两者兼有HSV-1感染。我们将注册50名将HSV-1传输到其合作伙伴生殖区域以收集口腔和生殖器拭子的人，并确定这两个地点的高脱水率是否与较短的HSV-1传输时间相关联。这些研究将共同帮助我们了解生殖器HSV-1感染的传播动力学，并将深入了解对HSV-1的生殖器免疫反应，以告知HSV疫苗设计。