IMMUNOBIOLOGY OF GENITAL HSV2 INFECTION

单纯疱疹病毒II型生殖器感染的自然史 豚鼠的疾病与人类相似。 阴道内注射后 接种动物发生自限性生殖器感染， 建立潜伏感染，然后表现出自发感染 症状性以及亚临床复发性疾病。 这些 HSV感染的各个方面可以通过临床疾病来量化 评分、病毒空斑滴定、外植体共培养和HSV DNA 杂交方法 利用这种特征鲜明的生殖器模型 HSV2疾病，我们建议评估免疫功能， 改变急性感染或改变复发模式。 到 为了实现这些目标，我们开发了针对HSV特异性的检测方法， 细胞介导的免疫功能，包括自然杀伤（NK）细胞 细胞毒性，抗体依赖性细胞毒性（ADCC）， 淋巴细胞胚细胞生成或迟发性超敏反应，以及 体液免疫，包括中和、ADCC和抗 特异性HSV多肽。 此外，我们还在开发 以评价细胞毒性T细胞活性。 我们将利用 远交种哈特利的急性疾病的严重程度 豚鼠以及年龄和品系相关的差异， 研究可能导致这些疾病的免疫因素 差异 同样，我们将使用变量recurrence 远系繁殖的哈特利动物和 显著较低（与Hartley动物相比）的复发模式 在品系2豚鼠中检测免疫特性， 可能会影响疾病复发的模式。 我们将 确定菌株13和DHCBA菌株中的复发模式 动物，这将允许探索之间的关系， 豚鼠淋巴细胞抗原Ⅰ类和Ⅱ类复合物 和复发模式 因为豚鼠可以被流血的 我们将能够重复地跟踪具体的发展， 免疫功能，并将其与静止期或 在同一种动物身上反复出现。 生殖器带状疱疹模型 我们开发的疱疹允许解剖分离 不同阶段的初始生殖器感染， 研究被动获得抗体的能力，或 特异性免疫细胞，以修改感染的几个网站， 同样的动物。 我们还将利用亚基HSV糖蛋白 疫苗和HSV 1口腔感染模型，以更好地定义 这些基因修饰生殖器HSV 2位点和机制 感染.

The natural history of herpes simplex type II genital infection in guinea pigs is similar to human disease. After intravaginal inoculation animals develop a self-limited genital infection, establish latent infection and later exhibit spontaneous symptomatic, as well as subclinical recurrent disease. These aspects of HSV infection can be quantified by clinical illness score, virus plaque titration, explant cocultivation and HSV DNA hybridization. Utilizing this well characterized model of genital HSV2 disease we propose to evaluate immune functions that may alter the acute infection or modify the recurrence pattern. To accomplish these goals we have developed assays for HSV specific cell-mediated immune functions including natural killer (NK) cell cytotoxicity, antibody dependent cell cytotoxicity (ADCC), lymphocyte blastogenesis or delayed hypersensitivity as well as humoral immunity including neutralizing, ADCC, and antibody to specific HSV polypeptides. In addition we are developing assays to evaluate the cytotoxic t cell activity. We will take advantage of the variable severity of the acute disease in outbred Hartley guinea pigs as well as age and strain related differences to investigate immune factors that could account for these differences. Similarly, we will use the variable recurrence patterns that develop in outbred Hartley animals and the markedly lower (compared to Hartley animals) recurrence pattern in strain 2 guinea pigs to examine immune characteristics that might influence the pattern of recurrent disease. We will determine the recurrence pattern in strain 13 and DHCBA strain animals which will allow the exploration of relationship between class I and class II guinea pig lymphocyte antigen (GPLA) complex and the recurrence pattern. Because a guinea pig can be bled repetitively we will be able to follow the development of specific immune functions and relate these to periods of quiescence or recurrences in the same animal. The zosteriform model of genital herpes we have developed allows anatomic separation of the various stages of initial genital infection and will enable investigation of the ability of passively acquired antibody or specific immune cells to modify infection at several sites in the same animal. We will also utilize a subunit HSV glycoprotein vaccine and a model of HSV1 oral infection to better define the site and mechanisms by which these may modify genital HSV2 infections.