Genital papillomavirus infections are the most common sexually transmitted infections (STIs) among women in the United States and throughout the world. In addition to causing genital warts, persistent cervical infection with oncogenic alpha papillomaviruses can result in cervix cancer. Essentially all cases of cervix dysplasia and cancer are caused by specific types of human papillomavirus (HPV). Sexually transmitted genital papillomavirus requires a complex cellular environment which is not easily replicated in tissue culture or rodent models, limiting the study of the molecular events of HPV cervical infection, risk factors that lead to persistent infection and development and testing of novel prophylactic and therapeutic modalities. We have recently identified a novel primate model for cervicovaginal papillomavirus infection using female cynomolgus macaques. Studies indicate that these animals can develop PV-associated dysplastic and neoplastic cervical lesions similar to those found in women. We have identified specific macaque PV (MPV) types that are closely related phylogenetically to high-risk oncogenic HPV types and showed that a common persistent type of MPV called RhPV-d may be transmitted experimentally. This was demonstrated by identifying viral DNA and RNA in recipient animals. Recently, we have developed a serologic assay for RhPV-d and show seroconversion with experimental infection. Although prophylactic vaccines of HPV types 16 and 18 have been shown to prevent HPV infection and cervical cancer resulting from these specific types of HPV;however, high cost, lack of activity in already infected women, limited viral coverage, and requisite cold-chain have limited the use of these vaccines, particularly in developing nations where cervical cancer remains an urgent public health problem. The goal of this study is to develop the macaque model for widespread use in PV research for the scientific/medical community. To accomplish this within the context of an R21 Developmental Research Grant, we have the following specific aims: (1) To generate a renewable infectious stock of RhPV-d using two different experimental approaches;(2) to optimize experimental methods of papillomavirus infection in female macaques. This model should facilitate the understanding of genital papillomavirus pathogenesis, host immune response and development of strategies to reduce genital PV infection and PV-associated neoplasia. PUBLIC HEALTH RELEVANCE: Genital human papillomavirus (HPV) infections are the most common Sexually Transmitted Infections. Genital HPV infections can cause genital warts and genital cancers (e.g, cervical cancer). We propose to develop a novel macaque model of genital papillomavirus infection to allow studies on the natural history of genital papillomavirus infection and for testing new therapies and vaccines to reduce suffering and death in the human population from this infection.