Host Response and Pathogenesis in the Oral Cavity during SIV Infection

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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.