Conserved gammaherpesvirus kinase and histone variant H2AX facilitate gammaherpesvirus latency in vivo

Many herpesvirus-encoded protein kinases facilitate viral lytic replication Importantly, the role of viral kinases in herpesvirus latency is less clear Mouse gammaherpesvirus-68 (MHV68)-encoded protein kinase orf36 facilitates lytic replication in part through activation of the host DNA damage response (DDR) Here we show that MHV68 latency was attenuated in the absence of orf36 expression Unexpectedly, our study uncovered enzymatic activity-independent role of orf36 in the establishment of MHV68 latency following intraperitoneal route of infection H2AX. an important DDR protein, facilitates MHV68 lytic replication and may be directly phosphorylated by orf36 during lytic infection In this study, H2AX deficiency, whether systemic or limited to infected cells, attenuated the establishment of MHV68 latency in vivo Thus, our work reveals viral kinase-dependent regulation of gammaherpesvirus latency and illuminates a novel link between H2AX, a component of a tumor suppressor DDR network, and in vivo latency of a cancer-associated gammaherpesvirus (C) 2010 Published by Elsevier Inc