PAPILLOMAVIRUS ANIMAL MODEL FOR THERAPY EVALUATION

乳头瘤病毒感染是导致几个临床 重大疾病。 全球宫颈癌的年发病率 癌症约为450，000例， 乳头状瘤病毒（HPV）已被强烈暗示为最 一致确定的肿瘤病因学的辅助因子。 此外，HPV是尖锐湿疣的病原体 acuminatum是一种性传播感染，目前 生殖器疱疹的传播速度更快 这种情况的发生率 疾病在1966年至1981年间增加了500%（MMWR 32：306- 308，1983）。 尖锐湿疣的旺盛生长常见于 免疫抑制患者;那些免疫系统 由于怀孕等临时情况而受到抑制， 艾滋病患者和其他严重免疫缺陷者。 HPV也是复发性呼吸道乳头状瘤病的原因 (RRP)罕见（美国每年约有1500例新发病例） 但也是一种折磨儿童和成人的毁灭性感染。 除了支持有前途的治疗药物的临床试验外， 抗病毒物质计划（ASP）维护一个 各种人类感染的动物模型，其中 可以在临床试验之前评估实验性疗法。 有几种乳头瘤病毒感染的动物模型 与人类疾病有许多共同特征。 的目标 本合同为： 1. Shope乳头瘤病毒兔模型的使用和 人乳头瘤病毒感染裸小鼠异种移植模型 用于评估实验性抗病毒疗法。 2. 基础研究的自然史和发病机制 乳头状瘤病毒感染很可能表明 控制感染的策略。

Papillomavirus infections are responsible for several clinically important diseases. The annual worldwide incidence of cervical carcinoma is about 450,000 cases and prior infection with a human papillomavirus (HPV) has been strongly implicated as the most consistently identified cofactor in the etiology of the neoplasm. In addition, HPV is the causative agent of condyloma acuminatum, a sexually transmitted infection which is currently spreading more rapidly than genital herpes. The incidence of this disease increased 500% between 1966 and 1981 (MMWR 32:306- 308, 1983). Exuberant growths of condyloma are often seen in immunosuppressed patients; those whose immune systems are suppressed by temporary conditions such as pregnancy as well as AIDS patients and other seriously immune deficient individuals. HPV is also the cause of recurrent respiratory papillomatosis (RRP), a rare (approximately 1500 new cases per year in the U.S.) but devastating infection which afflicts children as well as adults. In addition to supporting clinical trials of promising therapeutic agents, the Antiviral Substances Program (ASP) maintains a variety of animal models of human infections in which experimental therapies can be evaluated prior to clinical trial. Several animal models of papillomavirus infections are available which share many features with human disease. The objectives of this contract are: 1. The use of the Shope papillomavirus rabbit model and the xenograft model of human papillomavirus infection of nude mice for evaluation of experimental antiviral therapies. 2. Basic research on the natural history and pathogenesis of papillomavirus infections that may well suggest successful strategies for controlling infection.