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.
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