HPV INFECTIVITY & PERSISTENCE IN EXPERIMENTALLY INFECTED FEMALE RHESUS MACAQUES

HPV 感染性

• 批准号: 7958649
• 负责人: Michelle A Ozbun
• 金额: $ 3.48万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958649
• 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; Disease Progression; Enzyme-Linked Immunosorbent Assay; Epithelium; Exposure to; Female; Funding; Genome; Grant; Human Papillomavirus; Human papillomavirus 16; Hyperkeratosis; Infection; Institution; Macaca mulatta; Modeling; Pap smear; Papillomavirus; Papillomavirus Infections; Pathology; Pilot Projects; Primates; Research; Research Personnel; Resources; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Serum; Source; Swab; Testing; Time; Transcript; United States National Institutes of Health; Vagina; Virion; Woman; 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 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.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 进行了一项试点研究，以开发恒河状乳头瘤病毒（RHPV）的生殖器感染模型，并评估其在非人类隐私的宫颈和肛门生殖道中的短期持久性。具有RHPV1基因组的感染性RHPV1病毒和伪造量被包装在HPV16 Capsids RHPV1HPV16中。将11只动物预先筛选，以通过PAP涂片，宫颈阴道镜，宫颈和肛门生殖器拭子预先存在RHPV感染，以表明PV诱导的病理学。 PCR和RT-PCR用于检测通过SWAB获得的细胞样品的RHPV基因组或转录本。通过ELISA测试血清的RHPV衣壳蛋白的抗体。在RHPV1暴露前28天给予五个RHPV1血清阴性和PCR阴性女性的pepo provera。用于促进阴道粘膜上皮细胞的变薄。当时，每只动物在RHPV1HPV16上都在静脉内和宫颈上挑战。在接种时，物理和宫颈检查显示了所有动物中阴道壁蜂蜜丧失的动物中对DEPO治疗的反应。接种后两个月（P.I.），4/5只动物（80％）和4个月P.I. 5/5只动物（100％）血清转化。所有五只动物的阴道壁略有至温和的蜂蜜的正常进展。在这五只动物之一中发现了略微肿大的淋巴结，并在3个月时增加了WBC。在5只动物中有2只观察到。在基线和两个月的所有五只动物的PAP分析均为正常。在第四月第四个月，一只动物表现出非典型的鳞状细胞，具有未知的显着性/低级SIL（ASC-US/ LGSIL）和三只具有广泛高肿瘤病的动物，与基线和低级SIL（LSIL）的显着变化表示四个月后RHPV1感染。这些具有LSIL的动物之一在6个月时解决了正常限制（WNL），这是感染HPV的妇女的普遍发现。一只动物在6个月的时间内连续三次取样表现出持续的LSIL。我们继续携带这些动物的采样有限，以观察是否会发生疾病进展。