Conserved gammaherpesvirus kinase and histone variant H2AX facilitate gammaherpesvirus latency in vivo. Virology 2010 Sep 15;405(1):50-61
Date
06/19/2010Pubmed ID
20557919DOI
10.1016/j.virol.2010.05.027Scopus ID
2-s2.0-77955515217 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
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.
Author List
Tarakanova VL, Stanitsa E, Leonardo SM, Bigley TM, Gauld SBAuthor
Vera Tarakanova PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsB-Lymphocytes
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Viral
Herpesviridae
Herpesviridae Infections
Histones
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation
Protein Kinases
Spleen
Viral Proteins
Virus Latency
