Epigenetic regulation of EBV and KSHV latency

Abstract

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.

Figure 1. Progressive Epigenetic Modifications Regulate Gammaherpesvirus Latency

Early stage histone modifications lead to metastable gene expression programs, which are reinforced by secondary higher-order chromosome conformations, including DNA looping. DNA methylation occurs more gradually and may take the place of repressive histone modifications to increase epigenetic stability.

Figure 2. Viral Encoded Epigenetic Modulators

(A) Cellular epigenetic regulators that interact with gammaherpesvirus chromosome organizing/episome maintenance proteins LANA and EBNA1. (B) Schematic of promoter regulatory interactions mediated by viral chromosome organizing factors for KSHV, LANA, and CTCF. (C) Promoter regulatory interactions for EBV in type I or type III latency conformations. OriP, EBNA1, and CTCF are highlighted.