γ-Herpesvirus-encoded miRNAs and their roles in viral biology and pathogenesis

To date, more than 200 viral miRNAs have been identified mostly from herpesviruses and this rapidly evolving field has recently been summarized in a number of excellent reviews (see [1,2]). Unique to gamma-herpesviruses, like Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus, is their ability to cause cancer. Here, we discuss gamma-herpesvirus-encoded miRNAs and focus on recent findings which support the hypothesis that viral miRNAs directly contribute to pathogenesis and tumorigenesis. The observations that KSHV mimics a human tumorigenic miRNA (hsa-miR-155), which is induced in EBV-infected cells and required for the survival of EBV-immortalized cells, lead to a number of studies demonstrating that perturbing this pathway induces B cell proliferation in vivo and immortalization of human B cells in vitro. Secondly, the application of state of the art ribonomics methods to globally identify viral miRNA targets in virus-infected tumor cells provides a rich resource to the KSHV and EBV fields and largely expanded our understanding on how viral miRNAs contribute to viral biology.