HERPESVIRUSES IN AIDS ASSOCIATED ORAL DISEASE

本研究探讨了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在病毒分子发病机制和宿主反应调节方面的影响。疱疹病毒引起持续感染，并在免疫抑制期间进入口腔，导致发病率增加，并且存在艾滋病定义的口腔病变。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情况，特别关注毛状白斑（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导致这些病理。该应用的中心假设是，疱疹病毒负荷随着免疫状态和药物治疗方案的变化而变化，口腔中的脱落和感染导致HLP和hiv - sgd等病理，这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的流行是否随免疫状态和抗艾滋病药物方案的变化而变化，其基础是一项横断面研究，该研究将从患病和非患病口腔组织、唾液和血液的组织样本中发现疱疹病毒的流行与1989/1990年和现在样本中记录的患者图表中的临床参数联系起来。病毒在这些不同标本中的流行程度将通过定量聚合酶链反应来确定。此外，本研究将确定疱疹病毒是否是hiv - sgd的病原，并在DNA和基因表达水平上表征感染。如果这些候选生物对hiv - sgd没有贡献，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。本研究将确定爱泼斯坦-巴尔病毒如何操纵细胞基因表达，从而导致HLP中检测到的特征性表型变化，并将这些分子发现与第一次AIM中确定的临床参数联系起来。建议的工作是多学科结合原则的病毒发病机制，临床研究设计和口腔流行病学。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先前在口腔医学和微生物学方面的培训，同时为她提供以患者为导向的临床研究为中心进行有意义研究的工具。

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.