HERPESVIRUSES IN AIDS ASSOCIATED ORAL DISEASE

艾滋病相关口腔疾病中的疱疹病毒

• 批准号: 6615645
• 负责人: Jennifer Y Webster-Cyriaque
• 金额: $ 11.56万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6615645
• 关键词: HIV infections; Herpesviridae disease; clinical research; human subject; opportunistic infections; oral leukoplakia; salivary disorder; virus load; virus virus interaction

This study addresses the molecular epidemiology of oral herpes viral infection in AIDS and seeks to understand the impact of these infections in terms of viral molecular pathogenesis and modulation of host response. Herpes viruses cause persistent infections and are shed into the oral cavity during immunosuppression resulting in increased morbidity and in the presence of AIDS defining oral lesions. The objective of these studies is to discern the prevalence of herpes viruses in saliva, blood, and oral disease, looking specifically at Hairy Leukoplakia (HLP) and (HIV) associated salivary gland disease to distinguish the character of infection, and to understand how the viruses modulate the host environment to cause these pathologies. The central hypothesis of this application is that herpes viral burdens vary with changes in immune status and drug regimen and that shedding and infection in the oral cavity results in pathologies such as HLP and HIVSGD that are a direct result of modulation of the cellular environment by these herpes viral pathogens. This study will determine whether herpes viral prevalence varies with changes in immune status and anti-AIDS drug regimen, based on a cross sectional studies that correlate herpes viral prevalence in tissue samples from diseased and non diseased oral tissues, saliva and blood to clinical parameters documented in patients charts from samples taken 1989/1990 and in present day specimens. Viral prevalence in these various specimens will be determined by quantitative polymerase chain reaction. Further, this study will determine if a herpes virus is the etiologic agent of HIVSGD and characterize the infection at the level of DNA and gene expression. If these candidate organisms do not contribute to HIVSGD we will attempt to isolate the agent using representational differential display and then characterize that infection. This study will determine how Epstein-Barr virus manipulates cellular gene expression to result in characteristic phenotypic changes detected in HLP and correlate these molecular findings with clinical parameters determined in the first AIM. The proposed work is multidisciplinary incorporating principles of viral pathogenesis, clinical research design and oral epidemiology. These studies will serve to advance the knowledge of oral herpes viral pathogenesis and will be carried out in collaboration with individuals who are leaders in the aforementioned three areas. Further, involvement in these studies will enhance the candidate's prior training in oral medicine and microbiology while equipping her with tools to perform meaningful studies centered around patient oriented clinical research.

本研究涉及艾滋病口腔疱疹病毒感染的分子流行病学，并试图了解这些感染的病毒分子发病机制和宿主反应的调制方面的影响。 疱疹病毒引起持续性感染，并在免疫抑制期间流入口腔，导致发病率增加，并在存在AIDS时定义口腔病变。 这些研究的目的是辨别疱疹病毒在唾液、血液和口腔疾病中的流行，特别是观察毛状白斑病（HLP）和（HIV）相关的唾液腺疾病，以区分感染的特征，并了解病毒如何调节宿主环境以引起这些病理。本申请的中心假设是疱疹病毒负荷随免疫状态和药物方案的变化而变化，并且口腔中的脱落和感染导致病理如HLP和HIVSGD，其是这些疱疹病毒病原体调节细胞环境的直接结果。 本研究将确定疱疹病毒流行率是否随免疫状态和抗艾滋病药物方案的变化而变化，该研究基于一项横断面研究，该研究将来自患病和非患病口腔组织、唾液和血液的组织样本中的疱疹病毒流行率与1989/1990年采集的样本和当今标本中记录的患者图表中的临床参数相关联。 将通过定量聚合酶链反应测定这些不同标本中的病毒流行率。 此外，这项研究将确定疱疹病毒是否是HIVSGD的病原体，并在DNA和基因表达水平上表征感染。 如果这些候选微生物不会导致HIVSGD，我们将尝试使用代表性差异显示分离病原体，然后表征感染。 本研究将确定EB病毒如何操纵细胞基因表达，导致HLP中检测到的特征性表型变化，并将这些分子结果与首次AIM中确定的临床参数相关联。 拟议的工作是多学科结合病毒发病机制，临床研究设计和口腔流行病学的原则。 这些研究将有助于提高对口腔疱疹病毒发病机制的认识，并将与上述三个领域的领导者合作进行。此外，参与这些研究将增强候选人在口腔医学和微生物学方面的先前培训，同时为她提供工具，以围绕以患者为中心的临床研究进行有意义的研究。