TY - JOUR T1 - A Viral microRNA Cluster Strongly Potentiates the Transforming Properties of a Human Herpesvirus A1 - Feederle, Regina A1 - Linnstaedt, Sarah D. A1 - Bannert, Helmut A1 - Lips, Helge A1 - Bencun, Maja A1 - Cullen, Bryan R. A1 - Delecluse, Henri-Jacques Y1 - 2011/02/17 N2 - Author Summary To persist in their hosts, herpes viruses must avoid recognition by the host's immune system. Down-regulation of viral antigen production through expression of viral miRNAs is a particularly elegant mechanism as these genetic elements do not encode proteins and remain therefore invisible to the immune system. Upon primary infection, Epstein-Barr virus (EBV) colonizes B cells and, through expression of its latent proteins, induces their continuous proliferation. The resulting expansion of infected B cells elicits a T cell response directed against the latent proteins that results in their elimination. Therefore, rapid proliferation of infected B cells, combined with reduced latent protein production, would facilitate establishment of EBV's viral reservoir before mounting of the immune response. Here, we find that a cluster of three microRNAs encoded near the EBV BHRF1 gene is crucial for efficient B cell transformation. In the absence of these genetic elements, infected B cells grow markedly more slowly. Furthermore, B cells exposed to an EBV mutant that lacks the BHRF1 microRNA cluster produced more latent proteins. Thus, the BHRF1 microRNA cluster possesses properties that potentiate EBV's oncogenic properties and therefore facilitate expansion of the EBV B cell reservoir. JF - PLOS Pathogens JA - PLOS Pathogens VL - 7 IS - 2 UR - https://doi.org/10.1371/journal.ppat.1001294 SP - e1001294 EP - PB - Public Library of Science M3 - doi:10.1371/journal.ppat.1001294 ER -