Characterization of epigenetic modifications during MHV68 lytic/latent infection

University Of Florida, Gainesville FL

Investigators

Abstract

Epigenetic modifications of histones plays a critical role in regulating the life cycle of gammaherpesviruses. An emerging theme in noncoding RNA (ncRNA) biology is a central role for these molecules in regulating epigenetic machinery. However, the role of ncRNAs in gammaherpesvirus infections, and the relationship between viral ncRNAs and epigenetics in the context of gammaherpesviruses, is poorly understood. Murine gammaherpesvirus 68 (MHV68) is genetically and pathogenically related to the human gammaherpesviruses, and infection of mice provides a unique system with which to study the interplay between epigenetics and viral ncRNAs. Previous studies have demonstrated that epigenetic modifications to herpesvirus genomes plays a central role in the regulation of lytic replication and the establishment/maintenance of EBV and KSHV latency. Recent reports have demonstrated that ncRNAs have the capacity to actively regulate epigenetic machinery. Such epi-ncRNAs are also likely to be crucial regulators of epigenetic modifications of histones associated with the viral genome and thus overall viral gene expression. Using MHV68-recombinant viruses lacking various ncRNAs, we have observed altered regulation of key components of the chromatin remodeling machinery, strongly suggesting that MHV68-encoded ncRNAs play an important role in regulation of epigenetically-regulated viral processes. Further defining the nature of this relationship should elucidate the roles for these ncRNAs in chronic gammaherpesvirus infection and pathogenesis.