Gammaherpesvirus gene expression and DNA synthesis are facilitated by viral protein kinase and histone variant H2AX. Virology 2011 Nov 25;420(2):73-81
Date
09/29/2011Pubmed ID
21943826Pubmed Central ID
PMC3204369DOI
10.1016/j.virol.2011.08.019Scopus ID
2-s2.0-80054053305 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
Gammaherpesvirus protein kinases are an attractive therapeutic target as they support lytic replication and latency. Via an unknown mechanism these kinases enhance expression of select viral genes and DNA synthesis. Importantly, the kinase phenotypes have not been examined in primary cell types. Mouse gammaherpesvirus-68 (MHV68) protein kinase orf36 activates the DNA damage response (DDR) and facilitates lytic replication in primary macrophages. Significantly, H2AX, a DDR component and putative orf36 substrate, enhances MHV68 replication. Here we report that orf36 facilitated expression of RTA, an immediate early MHV68 gene, and DNA synthesis during de novo infection of primary macrophages. H2AX expression supported efficient RTA transcription and phosphorylated H2AX associated with RTA promoter. Furthermore, viral DNA synthesis was attenuated in H2AX-deficient macrophages, suggesting that the DDR system was exploited throughout the replication cycle. The interactions between a cancer-associated gammaherpesvirus and host tumor suppressor system have important implications for the pathogenesis of gammaherpesvirus infection.
Author List
Mounce BC, Tsan FC, Droit L, Kohler S, Reitsma JM, Cirillo LA, Tarakanova VLAuthors
Lisa A. Cirillo PhD Assistant Dean, Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinVera Tarakanova PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsChromatin Immunoprecipitation
DNA Repair
DNA Replication
DNA, Viral
Gene Expression Regulation, Viral
Histones
Immediate-Early Proteins
Macrophages
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein Kinases
Rhadinovirus
Transcription, Genetic
Viral Proteins