Conserved gammaherpesvirus kinase and histone variant H2AX facilitate gammaherpesvirus latency in vivo
| Autor: | Tarin M. Bigley, Eleni S. Stanitsa, Steven M. Leonardo, Stephen B. Gauld, Vera L. Tarakanova |
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| Rok vydání: | 2010 |
| Předmět: |
Gene Expression Regulation
Viral DNA damage viruses Biology DNA damage response medicine.disease_cause Gene Expression Regulation Enzymologic Histones Mice Viral Proteins Virology medicine Animals H2AX Latency (engineering) Protein kinase A latency Herpesviridae Regulation of gene expression Mice Knockout Mutation B-Lymphocytes gammaherpesvirus Kinase Herpesviridae Infections Cell biology Virus Latency Mice Inbred C57BL Histone Lytic cycle biology.protein herpesvirus protein kinase Protein Kinases Spleen |
| Zdroj: | Virology. 405(1):50-61 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2010.05.027 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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