Malignant gliomas are the most common primary central nervous system tumors in humans. Our laboratory has obtained evidence indicating that human cytomegalovirus (HCMV), a ubiquitous herpesvirus, is strongly associated with malignant gliomas in vivo. HCMV can promote oncogenic transformation and can dysregulate key cellular pathways such as those affecting angiogenesis, invasion and cell cycle. Multiple strains of HCMV exist in the wild that have different genotypes and phenotypes. Cell mediated immune mechanisms, which can vary from individual to individual, are essential in preventing HCMV disease. Based on these observations, we hypothesize that HCMV infection of glioma cells promotes malignant glioma tumor progression. Further, we hypothesize that HCMV strains with increased oncogenic phenotypes may occur in the wild and may be able to promote glioma progression in individuals with relatively impaired cell mediated cell mediated immune systems, and that this could explain why a common virus is associated with a rare disease. To test this hypothesis, we have designed experiments with three aims: 1) to determine the role of HCMV infection on the angiogenic, invasive and cell cycle properties astrocyte-derived cells, 2) to determine whether glioma-derived HCMV strains possess distinct genotypes and/or gene expression patterns, and 3) to determine if patients with gliomas possess immunogenetic markers associated with an increased risk of HCMV related disease.
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