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

• HITS-CLIP and PAR-CLIP provide putative target lists for KSHV and EBV miRNAs.
• Both KSHV and EBV mimic host cellular miRNAs in lymphoid and endothelial cells.
• EBV and KSHV miRNAs regulate B cell proliferation and contribute to tumorigenesis.
• Although with different sequences γ-herpesvirus miRNAs target common cellular pathways.

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 and 2]). Unique to γ-herpesviruses, like Kaposi's sarcoma-associated herpesvirus and Epstein–Barr virus, is their ability to cause cancer. Here, we discuss γ-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.