Determining Viral Pathogenesis in HIV SGD

University Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

DESCRIPTION: (provided by applicant) Work in recent years has been directed to understanding the mechanisms of viral molecular pathogenesis in individuals with compromised immune systems. The long-range goal of this research is to understand mechanisms of viral molecular pathogenesis in oral disease that develops in immunocompromised patients. AIDS associated malignancies including Kaposi's Sarcoma and AIDS associated lymphoma are herpes virus associated and cause significant morbidity in these individuals. An increasing incidence in HIV-associated salivary gland disease (HIV SGD), a premalignant lesion, provides an opportunity to elucidate the pathogenesis of this oral infection and eventually target and implement appropriate interventions to decrease oral cavity morbidity associated with HIV SGD. The central hypothesis is that infection of the salivary glands with herpesviral agents results in HIV SGD, and that like AIDS lymphoma and Kaposi's Sarcoma, this pathology is a direct result of modulation of the cellular environment by herpesviral pathogens. This hypothesis-generating proposal seeks funds to allow us to refine hypotheses for subsequent studies regarding HIV SGD putative pathogens. At present there is not a good method for linking clinical disease to viral infection. A major limitation is often the size of the specimen. The ultimate goals of this small grant proposal are to develop and validate novel technologies that can facilitate rapid detection of these pathogens, their state of infection, and their gene transcription from the smallest (and least invasively-collected) specimen. These tools will allow us to the refine our hypothesis by determining herpesviral presence, genomic structure, and gene expression in HIV SGD.