Kaposi's sarcoma-associated herpesvirus (KSHV) causes cancer, most commonly in immuno-compromised individuals. The clinically most relevant KSHV-induced disease is Kaposi's sarcoma (KS), a complex tumor driven by KSHV-infected endothelial cells. Due to the AIDS epidemic, KS has become the most common cancer in parts of Africa. KSHV also infects B lymphocytes and can consequently cause B cell lymphomas, including primary effusion lymphoma. KSHV constitutively expresses viral microRNAs from 12 precursors, suggesting a role of these microRNAs in viral replication and pathogenesis.
microRNAs are ~22 nucleotide regulatory RNAs expressed by animals, plants and some viruses, particularly herpesviruses. As components of the RNA-induced silencing complex (RISC), microRNAs guide the repression of mRNAs bearing sequences with partial complementarity to the microRNA. This effect is most commonly mediated through base pairing between the "seed region" of the microRNA, spanning nucleotides 2-7, and sites located in the 3'UTRs of target mRNAs. Because there are several hundred known mammalian microRNAs and each can regulate several hundred mRNAs, it is now thought that most mRNAs are regulated by microRNAs in some biological context.
Our lab is currently pursuing the comprehensive identification of mRNA targets of the KSHV microRNAs in primary effusion lymphoma cell lines and KSHV-infected endothelial cells.
Our data suggests that, together, the KSHV microRNAs directly target hundreds of cellular mRNAs encoding proteins with roles in several different biological pathways. Our goal is to use this knowledge to characterize the most important functions of the KSHV microRNAs. Download our findings via our Data page.