Epidemiology and Immunobiology of HSV Infection

关于美国青少年中2型单纯疱疹病毒感染率的数据有限。此外，为控制感染和促进发病机制提供基础的初始免疫应答的功能机制和分子靶点在很大程度上是未知的。与老年人相比，青少年在免疫方面可能更“幼稚”，更有可能被诊断为原发性感染，对他们的感染进行检查，对于评估与最初感染、传播或发展为更严重的后遗症（包括复发性溃疡）相关的因素之间的相互作用具有重要意义。因此，青少年提供了一个独特的机会来审查那些与疫苗研制和治疗直接相关的因素。确定青少年中1型单纯疱疹病毒感染的流行情况，以及1型单纯疱疹病毒和2型单纯疱疹病毒血清患病率之间的相互关系（如果有的话），将为最佳的单纯疱疹病毒疫苗策略提供进一步的重要信息。具体来说，我们的目标是：1。目的：确定性活跃的非裔美国青少年中流行和发生HSV-1和HSV-2感染的社会人口学和行为危险因素。2. 确定细胞介导免疫反应的自然史与感染个体中HSV临床表现的关系。我们将评估CD4 t细胞对HSV-1和HSV-2共同的糖蛋白（gB和gD）、类型特异性gG2蛋白和hsv感染细胞抗原的识别，以及对这些抗原刺激的Th1和Th2细胞因子的反应。3. 确定在研究过程中，在两型单纯疱疹病毒血清学状况不一致的青少年及其性伴侣之间传播2型单纯疱疹病毒的免疫危险因素。将使用基于gg2的类型特异性血清学检测评估传播模式，然后将其与HSV感染的临床病史、异源病毒抗体和关系持续时间进行关联。

There are limited data regarding the prevalence of HSV-2 infections among US adolescents. In addition, the functional mechanism and molecular targets of the initial immune responses that provide the foundation for controlling infection and promoting pathogenesis is largely unknown. Examining infection in adolescents who are presumably more immunologically "naive" and more likely to be diagnosed with a primary infection, compared to older individuals provides an important for evaluating the interaction among factors related to initial acquisition of infection, transmission, or progression to more severe sequelae including recurrent ulcers. Thus, adolescents present a unique opportunity to examine those factors which have direct relevance to vaccine development and treatment. Determining the prevalence of HSV-1 infection among adolescents and the interrelationship, if any, between seroprevalence of HSV-1 and HSV-2 will provide further important information regarding optimal HSV vaccine strategies. Specifically our aims are: 1. To determine sociodemographic and behavioral risk factors for prevalent and incident HSV-1 and HSV-2 infection among sexually active African-American adolescents. 2. To determine the natural history of cellular mediated immune responses in relation to clinical manifestations of HSV among infected individuals. We will assess the CD4 T-cell recognition of glycoproteins common to HSV-1 and HSV-2 (gB and gD), the type-specific gG2 protein and HSV-infected cell antigen, along with the Th1 and Th2 cytokine responses to stimulation with these antigens. 3. To determine immunologic risk factors for transmission of HSV-2 between adolescents and their sex partners over the course of the study among couples who are discordant on their HSV-2 serologic status. Transmission patterns will be assessed using gG2-based type-specific serologic assay, and then correlated with clinical histories of HSV infection, antibodies to heterologous virus, and duration of relationships.