The opportunities and challenges of epigenetic approaches to manage herpes simplex infections.

Introduction: Despite the existence of antivirals that potently and efficiently inhibit the replication of herpes simplex virus 1 and 2 (HSV-1, -2), their ability to establish and maintain, and reactivate from, latency has precluded the development of curative therapies. Several groups are exploring the opportunities of targeting epigenetic regulation to permanently silence latent HSV genomes or induce their simultaneous reactivation in the presence of antivirals to flush the latent reservoirs, as has been explored for HIV.

Areas Covered: This review covers the basic principles of epigenetic regulation with an emphasis on those mechanisms relevant to the regulation of herpes simplex viruses, as well as the current knowledge on the regulation of lytic infections and the establishment and maintenance of, and reactivation from, latency, with an emphasis on epigenetic regulation.

Histone H2A variant H2A.B is enriched in transcriptionally active and replicating HSV-1 lytic chromatin.

Unlabelled: Herpes simplex virus 1 (HSV-1) transcription is restricted in latently infected neurons and the genomes are in mostly silenced chromatin, whereas all viral genes are transcribed in lytically infected cells, in which the genomes are dynamically chromatinized. Epigenetic regulation modulates HSV-1 transcription during lytic, latent, and reactivating infections but the precise mechanisms are not fully defined. Nucleosomes are dynamic: they slide, breathe, assemble, and disassemble.

Histone H2A variant H2A.B is enriched in transcriptionally active HSV-1 lytic chromatin.

Unlabelled: Herpes simplex virus 1 (HSV-1) transcription is restricted in latently infected neurons and the genomes are in mostly silenced chromatin, whereas all viral genes are transcribed in lytically infected cells, in which the genomes are dynamically chromatinized. Epigenetic regulation modulates HSV-1 transcription during lytic, latent, and reactivating infections, but the precise mechanisms are not fully defined. Nucleosomes are dynamic; they slide, breathe, assemble and disassemble.