Kaposi’s Sarcoma Associated Herpesvirus modulates the expression of Human Endogenous Viruses

Human endogenous viral elements (EVE) or transposable elements (TEs) are mobile genomic sequences of viral origin that are able to change their position within the genome. They are ubiquitous in eukaryotic genomes, occupying about 45% of the human genome. TEs have been linked with a variety of disorders and malignancies, though the precise nature of their contribution to many of them has yet to be elucidated. The effect of Kaposi’s sarcoma associated herpesvirus (KSHV, HHV-8) on cellular gene expression was extensively studied, but our knowledge on the effect of KSHV on TEs is very limited. Here, to study the effect of KSHV on the expression of TEs, we have done transcriptome analysis of KSHV-associated primary effusion lymphoma (PEL) cells (BCBL1 and BC3) and de-novo infected B-cell lymphoma BJAB (BJAB219), by next-generation RNA sequencing (RNA-seq). We found that large number of TEs are differentially expressed in PEL cells, which includes LTR transposons, LINEs, SINEs, DNA transposons and DNA repeat elements. In de-novo infected BJAB219 cells we also detected differentially expressed TEs compared to un-infected controls, although to a lesser extent. The epigenetic changes imposed by KSHV on the host cells seems to play a major role in the expression of these TEs. In conclusion, our results demonstrate that KSHV infection modulates the expression of many TEs, and in chronically infected PEL cells many more TEs are upregulated. Up-regulation of these mobile elements during chronic infection might contribute to enhanced transposition events and therefore induce genetic instability that may play a crucial role in KSHV tumorigenesis.