IMMUNOBIOLOGY OF GENITAL HSV2 INFECTION

年单纯疱疹病毒II型生殖器感染的自然病史 豚鼠类似于人类的疾病。经阴道后 接种疫苗的动物会产生一种自我限制的生殖器感染， 建立潜伏感染，后来表现为自发性 有症状的，以及亚临床复发性疾病。这些 单纯疱疹病毒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。利用这种很有特色的生殖器模型 HSV2疾病我们建议评估免疫功能，可能 改变急性感染或修改复发模式。至 为了实现这些目标，我们开发了针对HSV特异性的检测方法 包括自然杀伤(NK)细胞在内的细胞免疫功能 细胞毒性、抗体依赖细胞毒性(ADCC)、 淋巴细胞转化或迟发型超敏反应以及 体液免疫，包括中和、ADCC和抗体 HSV特异性多肽。此外，我们正在开发化验方法 检测细胞毒T细胞活性。我们会利用这个优势 哈特莱野马急性疾病的不同严重程度 豚鼠以及与年龄和应变相关的差异 调查可能解释这些的免疫因素 不同之处。同样，我们将使用变量Recurn 在近亲繁殖的哈特利动物和 (与Hartley动物相比)复发率显著降低 在品系2的豚鼠身上检测免疫特性 可能会影响复发疾病的模式。我们会 确定菌株13和DHCBA菌株的复发模式 这将允许探索动物之间的关系 豚鼠淋巴细胞抗原I类和II类复合体 以及反复发作的模式。因为一只豚鼠可以流血 反复我们将能够跟踪具体的发展 免疫功能，并与静止期或 在同一只动物身上复发。生殖器带状模型 我们开发的疱疹允许解剖分离 初始生殖器感染的不同阶段，并将使 被动获得性抗体免疫应答能力的研究 特定的免疫细胞，以修改在几个地点的感染 同样的动物。我们还将利用HSV糖蛋白亚单位 疫苗和HSV1口腔感染模型以更好地定义 这些病毒可能改变生殖器HSV2的部位和机制 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.