RHPV INFECTIVITY & PERSISTENCE IN EXPERIMENTALLY INFECTED FEMALE RHESUS MACAQUES

RHPV 感染性

• 批准号: 7716289
• 负责人: Michelle A Ozbun
• 金额: $ 1.39万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-21 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716289
• 关键词: Animals; Antibodies; Atypical Squamous Cell; Capsid; Capsid Proteins; Cells; Cervical; Cervix Uteri; Colposcopy; Computer Retrieval of Information on Scientific Projects Database; Depo Provera; Enzyme-Linked Immunosorbent Assay; Epithelium; Exposure to; Female; Funding; Genome; Grant; Human papillomavirus 16; Hyperkeratosis; Institution; Lesion; Macaca mulatta; Modeling; Pap smear; Papillomavirus; Papillomavirus Infections; Pathology; Pilot Projects; Polymerase Chain Reaction; Research; Research Personnel; Resources; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Serum; Source; Swab; Testing; Time; Transcript; United States National Institutes of Health; Vagina; Virion; White Blood Cell Count Increased; day; follow-up; genital infection; keratinization; lymph nodes; nonhuman primate; response

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 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.), there was a normal progression with slight to mild cornification of the vaginal walls for all five animals. None, however, showed any visible cervical lesions. 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 showed extensive hyperkeratosis, a significant change from the baseline results. Pathology is currently performing a more extensive follow-up assessment. A final 6 month p.i. examination and sampling timepoint will occur in January, 2008. This time point will allow us to evaluate if a progression in pathology has occurred in the papilloma virus inoculated animals.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 中心，不一定是研究者的机构。 进行了一项初步研究，以开发恒河猴乳头瘤病毒 (RhPV) 生殖器感染的恒河猴模型，并评估其在非人灵长类动物宫颈和肛门生殖道中的短期持久性，将具有 RhPV1 基因组的感染性 RhPV1 病毒粒子和假病毒粒子包装在 HPV16 衣壳 RhPV1HPV16 中。通过子宫颈抹片检查、宫颈阴道镜检查、使用 PCR 和 RT-PCR 检测宫颈和肛门生殖器拭子，以检测拭子获得的细胞样本中的 RhPV 基因组或转录物，并通过 ELISA 检测血清中的 RhPV 衣壳蛋白抗体。普罗韦拉??在接触 RhPV1 前 28 天施用，以促进阴道粘膜上皮变薄。当时，每只动物都接受 RhPV1HPV16 的阴道内和宫颈攻击。在接种时，体检和宫颈检查显示所有动物对 Depo 治疗有反应。到接种后两个月（p.i.），所有五只动物的阴道壁角化均出现正常进展，轻微至轻度角化。然而，五只动物中的一只没有发现任何明显的淋巴结病变，并且在注射后 3 个月时，观察到 5 只动物中的 2 只在基线时白细胞计数正常。接种后第 1 个月和第 2 个月，接种后第 4 个月，一只动物表现出意义不明的非典型鳞状细胞/低级 SIL (ASC-US/LGSIL)，三只动物表现出广泛的角化过度，这是与病理学目前正在进行更广泛的随访评估，最后 6 个月的检查和采样时间点将在 2008 年 1 月进行。该时间点将允许我们评估乳头状瘤是否发生病理进展。病毒接种的动物。