Host Response and Pathogenesis in the Oral Cavity during SIV Infection

描述（由申请人提供）：HIV感染患者发展为艾滋病的特点是出现机会性继发性感染和免疫抑制，这是由于CD4+辅助性T细胞功能的破坏性丧失。在直接暴露于病原体的隔室中，口腔黏膜特别容易受到感染，因为它直接暴露于来自饮食和空气传播的微生物。口腔慢性继发性感染已知起源于多种真菌、细菌、病毒和真核生物。合乎逻辑的是，组织形态和功能恶化的外在迹象是由局部环境分子谱的明显变化引起的，并且我们对抗艾滋病毒疾病进展的能力的提高取决于对这种转变性质的理解。然而，口腔发病机制、机会性继发感染的出现和发展为艾滋病之间的关系仍未得到充分研究。提出的研究将阐明宿主-病毒相互作用的细节，并通过将功能基因表达谱的变化与疾病进展的不同表型相关联系起来，增加我们对SIV感染所有阶段的口腔致病机制和免疫学的认识。将采用分离上皮细胞和确定基因表达谱的创新生物技术。对急性、慢性和艾滋病阶段感染的口腔生物学进行全面的临床和分子分析，将提供有关口腔免疫功能的前所未有的信息，确定SIV疾病进展的相关生物标志物，并为发展假设奠定基础，以检验未来的研究。

DESCRIPTION (provided by applicant): Progression to AIDS in HIV infected patients is characterized by the emergence of opportunistic secondary infections and immunosuppression that result from a devastating loss of CD4+ helper T cell function. Among the compartments with direct exposure to pathogens the oral mucosa is particularly susceptible, being directly exposed to microorganisms from dietary and air-borne sources. Chronic secondary infections in the oral cavity are known to originate from a variety of fungal, bacterial, viral, and eukaryotic organisms. It is logical that the outward signs of deterioration in tissue morphology and function are preceded and driven by distinct changes in the molecular profile of the local environment, and that improvements in our ability to combat HIV disease progression are dependent on understanding the nature of this transition. The relationship between pathogenesis of the oral cavity, the emergence of opportunistic secondary infections, and progression to AIDS, however, remains under-investigated. The studies proposed will elucidate details of host-virus interaction and increase our knowledge of pathogenic mechanisms and immunology in the oral cavity at all stages of SIV infection by linking changes in functional gene expression profiles with distinct phenotypic correlates of disease progression. Innovative biotechnologies for isolating epithelial cells and determining gene expression profiles will be employed. Comprehensive clinical and molecular analyses of oral biology in acute, chronic, and AIDS stage infections will provide unprecedented information about immune functions in the oral cavity, identify correlative biomarkers of SIV disease progression, and lay the ground work for developing hypotheses to test future studies.