1887

Abstract

We have used a spleen explant model to investigate mechanisms of murine cytomegalovirus latency and reactivation. Induction of immediate-early () gene expression occurs in explants after approximately 9 days in culture and virus reactivation follows induction of gene expression with kinetics similar to that of productive infection . This occurs independently of TNF receptor signalling. Treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine and the histone deacetylase inhibitor trichostatin A results in more rapid induction of gene expression and reactivation of virus. Despite these results, which suggest a role for DNA methylation in maintenance of viral latency, we find that the major immediate-early promoter/enhancer is not methylated in latently infected mice. Our results support the hypothesis that latency is maintained by epigenetic control of gene expression, and that induction of gene expression leads to reactivation of virus, but suggest that these are not controlled by DNA methylation.

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2007-04-01
2024-04-20
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