We have several projects aimed at characterizing how therapeutics targeting host and viral processes impact EBV-associated diseases. In a collaboration with Evrys Bio, we are defining the role of sirtuin 2 antagonists in suppressing EBV latency and lytic replication. This work is based on recent evidence for a broad-spectrum antiviral role for sirtuin 2 antagonism defined by the Shenk laboratory and others. In a second collaborative effort with industry (Viracta), we are defining the mechanism by which EBV latently infected tumors are sensitized to killing by ganciclovir using histone deacetylase inhibition to promote lytic reactivation. This so-called “kick and kill” strategy has shown great promise clinically and could provide a paradigm for other EBV-associated diseases as well as other latent viral infections such as HIV. A final translational study we are pursuing is an assessment of the humoral immune response to EBV in lung transplant patients that develop EBV viremia or post-transplant lymphoma. While T cell responses have been characterized in this disease and can be therapeutically relevant, little is known about the role of humoral immunity and the potential for hyper-gamma globulin against EBV or vaccination to prevent poor outcomes associated with EBV reactivation in the immune suppressed.
Ashley Lauren Nico
