Epigenetic regulation of EBV and KSHV latency

•Gammaherpesviruses can adopt a variety of gene expression patterns during latent infection.•Gene expression patterns correlate with changes in epigenetic modifications, including DNA methylation, histone modifications, and chromosome conformations.•Viral episome maintenance proteins play a central role in epigenetic regulation and chromosome organization.

The gammaherpesviruses are unique for their capacity to establish a variety of gene expression programs during latent and lytic infection. This capacity enables the virus to control host-cell proliferation, prevent programmed cell death, elude immune cell detection, and ultimately adapt to a wide range of environmental and developmental changes in the host cell. This remarkable plasticity of gene expression results from the combined functionalities of viral and host factors that biochemically remodel and epigenetically modify the viral chromosome. These epigenetic modifications range from primary DNA methylations, to chromatin protein post-translational modifications, to higher-order chromosome conformations. In addition, gammaherpesviruses have acquired specialized tools to modulate the epigenetic processes that promote viral genome propagation and host-cell survival.