DNA CpG HYPO-METHYLATION IMPOSED ON THE HUMAN GENOME BY KAPOSI’S SARCOMA ASSOCIATED HERPESVIRUS

Kaposi’s sarcoma-associated herpesvirus (KSHV) is one of the seven known human cancer causing viruses and is also known by its association with primary effusion lymphoma and Multicentric Castlemans Disease. DNA methylation is crucial for normal function of the human genome. CpG DNA methylation at promoters is associated with gene silencing. While several promoter hyper-methylation in KSHV infected cells were studied, not much is understood regarding promoter hypo-methylation and subsequent gene expression up-regulation imposed on the human genome by KSHV latent infection. In this study we aim to explore the effects of promoter hypo-methylation imposed by KSHV on host gene expression. Moreover, we aim to understand whether global genome hypo-methylation caused by KSHV acquired randomly throughout the genome of the host or rather has a specific footprint. We have performed a genome wide CpG methylation analysis on several uninfected and KSHV-infected cells including KSHV-associated malignancies. Our results revealed dramatic changes in methylation patterns between CpGs located on CpG islands (CpG-enriched sequences) compared to non CpG island in KSHV infected cells suggesting that KSHV tends to de-methylate none CpG island areas during chronic infection. Furthermore, we found a panel of hypo-methylated cellular promoters in KSHV infected PEL cells associated with transcription up-regulation of their regulated genes. This study may contribute to our understanding of the relationship between epigenetic changes caused by KSHV infection and tumorogenesis.