This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A pilot study was done to develop a rhesus model of genital infection with rhesus papillomavirus (RhPV) and assess their short-term persistence in the cervices and anogenital tracts of nonhuman primates. Infectious RhPV1 virions and pseudovirions with RhPV1 genome were packaged in HPV16 capsids RhPV1HPV16. Eleven animals were prescreened for pre-existing RhPV infections by Pap smear, cervical colposcopy, cervical and anogenital swabs to indicate PV-induced pathology. PCR and RT-PCR was used to detect RhPV genomes or transcripts from cell samples obtained by swab. Sera was tested by ELISA for antibodies to RhPV capsid proteins. Five RhPV1 seronegative and PCR negative females had 30mg Depo Provera? administered 28 days prior to RhPV1 exposure to promote thinning of the vaginal mucosal epithelium. At that time, each animal was intravaginally and cervically challenged with RhPV1HPV16. At the time of inoculation, physical and cervical exams showed response to Depo treatment in all animals with loss of vaginal wall cornification in all animals. By two months post inoculation (p.i.), 4/5 animals (80%) and by 4 months p.i. 5/5 animals (100%) seroconverted. There was a normal progression with slight to mild cornification of the vaginal walls for all five animals. Slightly enlarged lymph nodes were noted in one of the five animals, and increased WBC at 3 months p.i. was observed in 2 of 5 animals. PAP analysis was normal for all five animals at baseline, one and two months p.i. At month four p.i., one animal demonstrated atypical squamous cells of unknown significance/low grade SIL (ASC-US/ LGSIL) and three animals with extensive hyperkeratosis, a significant change from baseline and low grade SIL (LSIL) indicative of an RhPV1 infection at four months. One of these animals with LSIL resolved to within normal limits (WNL) at 6 months, a common finding for women infected with HPV. One animal demonstrated persistent LSIL in three consecutive sampling over the 6 month period. We have continued to carry these animals with limited sampling to observe if disease progression will occur.
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