ART On Oral Tissue Growth, Function, and HPV Infections

口腔组织生长、功能和 HPV 感染的 ART

基本信息

批准号：
7277967
负责人：
Craig M Meyers
金额：
$ 34.74万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-10 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7277967
关键词：
AIDS/HIV problem Accidents Acquired Immunodeficiency Syndrome Adherence Adverse effects Affect Anti-Retroviral Agents Area Benign Biology CD4 Lymphocyte Count Cell Line Cessation of life Clinical Trials Condition Death Rate Defect Development Differentiation and Growth Dose Drug resistance Epidemic Epithelial Epithelial Cells Epithelium Frequencies Genotype Gingiva Goals Growth HIV HIV Infections HIV drug resistance Hairy Leukoplakia Heart Diseases Highly Active Antiretroviral Therapy Human Development Human Papillomavirus Human papilloma virus 31 Human papilloma virus infection Human papillomavirus 16 Human papillomavirus 18 Incidence Infection Knowledge Laboratories Lead Lesion Life Cycle Stages Link Maintenance Malignant Neoplasms Maps Mean Survival Times Mental Health Modeling Natural History Nature Oral Oral Manifestations Oral Pathology Oral candidiasis Oral cavity Oral health Oral mucous membrane structure Palate Kaposi&apos s Sarcoma Pathology Patients Periodontitis Pharmaceutical Preparations Physiological Principal Investigator Relapse Reporting Request for Applications Risk Site Structure Study models System Technology Testing Tissues Tonsil Treatment Protocols United States United States National Institutes of Health Variant Viral Virion Virus Wound Healing antiretroviral therapy base design experience human papilloma virus oncogene in vitro Model in vivo oral cavity epithelium oral condition oral infection oral lesion oral tissue oral wart programs response tissue culture

项目摘要

DESCRIPTION (provided by applicant): Use of highly active antiretroviral therapy (HAART) has made HIV/AIDS a manageable condition. Oral manifestations are often the earliest and most important indicator of HIV infections. Oral health is significantly linked to both physical and mental health improvement, and adverse oral health can lead to incomplete adherence to treatment regimens risking relapse in the patient and increasing the potential for development of drug resistance viruses. Use of HAART has resulted in a significant reduction in serious adverse oral conditions such as oral hairy leukoplakia, necrotizing ulcerative periodontitis, and oral candidiasis. Patients taking antiretroviral therapy (ART) have shown a significant increase in the development of HPV oral warts; particularly in patients presenting increased CD4 cell counts and reduced HIV load. We hypothesize that ART use is directly related to the increase of HPV oral lesions. To understand how ART is affecting the increase in oral lesions several important gaps in our knowledge need to be filled in. All of our studies will depend on using our three-dimensional organotypic raft culture system. Raft culture tissue has been to shown faithfully mimic its in vivo counterpart and represents a physiological relevant in vitro model. We have nearly 20 years experience using raft culture technology. Specific Aim 1 proposes to investigate the effect of ART on oral epithelial growth, differentiation, and wound healing. Adverse effects of ART on growth, differentiation, and wound healing would have a negative impact on oral health and provide mechanisms for observed changes in HPV infection and biology. Tonsil, buccal, and gingival epithelium will be studied. Specific Aim 2 proposes to study the replication of HPV in oral epithelium. Presently, it is not known if oral epithelium is permissive for replication of infectious HPV and what effect ART has on HPV permissive replication. If oral tissue is defective for permissive replication then Aim 2 is designed to define the nature of the defect in the viral life cycle. Productive oral lesions would make the oral cavity a site for the potential spread of HPV. In Aim 2 we will also investigate if ART is able to increase the infectivity of oral epithelial cells providing a mechanism for the increase in oral lesions seen in HIV/AIDS patients using HAART. Specific Aim 3 proposes to define the differentiation-dependent life cycle of HPV32 and HPV16 oral epithelium and test the effects of ART on their life cycles. Presently, nothing is known in any system about the life cycle of HPV32 and little is know about the life cycle of HPV16 in oral epithelial tissues. Our studies will provide an extensive map of the life cycles these two HPVs in oral epithelium and how ART impinges on their life cycles. We hypothesize that some of the effects of ART will be related to pathology of the infections, such as increases in HPV oncogenes E6 and E7 expression.

描述（由申请人提供）：使用高效抗逆转录病毒疗法（HAART）使艾滋病毒/艾滋病成为可控制的疾病。口腔表现往往是艾滋病毒感染的最早和最重要的指标。口腔健康与身心健康的改善密切相关，不良的口腔健康可能导致患者不完全遵守治疗方案，从而导致患者出现复发风险，并增加产生耐药病毒的可能性。使用HAART可显着减少严重不良口腔疾病，如口腔毛状白斑、坏死性溃疡性牙周炎和口腔念珠菌病。接受抗逆转录病毒治疗 (ART) 的患者 HPV 口腔疣的发生率显着增加；特别是在 CD4 细胞计数增加和 HIV 载量减少的患者中。我们假设 ART 的使用与 HPV 口腔病变的增加直接相关。为了了解 ART 如何影响口腔病变的增加，需要填补我们知识中的几个重要空白。我们所有的研究都将取决于使用我们的三维器官筏培养系统。筏培养组织已被证明忠实地模仿了其体内对应物，并代表了生理相关的体外模型。我们拥有近20年使用筏式养殖技术的经验。具体目标 1 建议研究 ART 对口腔上皮生长、分化和伤口愈合的影响。 ART 对生长、分化和伤口愈合的不利影响将对口腔健康产生负面影响，并为观察到的 HPV 感染和生物学变化提供机制。将研究扁桃体、颊和牙龈上皮。具体目标 2 建议研究 HPV 在口腔上皮细胞中的复制。目前，尚不清楚口腔上皮是否允许传染性 HPV 复制，以及 ART 对 HPV 允许复制有何影响。如果口腔组织存在复制缺陷，则目标 2 旨在定义病毒生命周期中缺陷的性质。产生性口腔病变会使口腔成为 HPV 潜在传播的场所。在目标 2 中，我们还将研究 ART 是否能够增加口腔上皮细胞的感染性，从而为使用 HAART 的 HIV/AIDS 患者口腔病变增加提供机制。具体目标 3 建议定义 HPV32 和 HPV16 口腔上皮的分化依赖性生命周期，并测试 ART 对它们生命周期的影响。目前，对于任何系统中 HPV32 的生命周期一无所知，而对于口腔上皮组织中 HPV16 的生命周期知之甚少。我们的研究将提供口腔上皮细胞中这两种 HPV 生命周期的广泛图谱，以及 ART 如何影响它们的生命周期。我们假设 ART 的一些影响与感染的病理学有关，例如 HPV 癌基因 E6 和 E7 表达的增加。