Role of viral microRNAs in Kaposi´s Sarcoma-associated Herpesvirus (KSHV) infection and KSHV-associated Disease

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Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of several tumors of endothelial and B cell origin. The majority of tumor cells in these malignancies are in a latent state of infection, a stage of the viral lifecycle during which only a few viral genes are expressed. Consequently, it is thought that latency genes play a major role in the onset and/or progression of tumorigenesis. Recently, we and others have discovered several latently expressed KSHV-microRNAs. MicroRNAs, a novel class of small RNAs able to downregulate mRNA expression, have emerged as important regulators of many cellular processes such as differentiation, proliferation and apoptosis. Furthermore, microRNAs are frequently deregulated in human cancers, and recent evidence suggest they can act as tumor suppressors as well as proto-oncogenes. We hypothesize that KSHV-encoded microRNAs play a crucial role in the viral lifecycle and furthermore might contribute to the pathogenesis of KSHV-associated disease. The proposed project aims at elucidating the functions of KSHV-microRNAs by i) identifying cellular mRNA targets, ii) investigating phenotypic consequences of microRNA expression and iii) defining the importance of KSHV microRNAs during de novo infection, latency establishment and lytic replication.