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：
8890054
负责人：
CHRISTINE MICHELLE JOHNSTON
金额：
$ 15.7万
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 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8890054
关键词：
Accounting Address Affect American Anatomy Antigens Area Biopsy Blood CCR5 gene CD4 Positive T Lymphocytes CD8B1 gene 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 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 Shedding Work Youth base clinical epidemiology co-infection cohort density evidence base genital herpes genital infection insight neonate peripheral blood receptor response 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.

1 型单纯疱疹病毒 (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 的自然史尚未得到表征。我们缺乏以下方面的知识：1）解剖部位初次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感染 HIV 风险的潜力； 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传播模式。为了弥补这些差距，我们建议：目标 1. 明确感染第一年口腔和生殖器 HSV-1 脱落的自然史。我们假设感染后第一年生殖器脱落率将急剧下降，这可能表明对 HSV-1 的免疫反应成功发展。我们将招募 100 名实验室记录有原发性生殖器 HSV-1 感染的人，通过为期 30 天的口腔和生殖器自我拭子研究，测量感染后 2 个月和 11 个月时生殖器和口腔 HSV-1 的脱落情况。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 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 细胞将在原发性生殖器病变部位持续存在数月，并且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落过程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续性（通过 CD4 和 CDS T 细胞的浓度进行测量）。目标 3. 确定传播伙伴是否在口腔或生殖器部位或两者都有 HSV-1 感染。我们将招募 50 名曾将 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，并确定任一部位的高脱落率是否与 HSV-1 传播给易感性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 感染的传播动态，并将深入了解生殖器对 HSV-1 的免疫反应，为 HSV 疫苗设计提供信息。