Dynamic modulation of HSV chromatin drives initiation of infection and provides targets for epigenetic therapies

- Chromatin modulation regulates HSV infection and latency-reactivation cycles.
- Multiple factors impact the initial chromatin state of the infecting viral genome.
- Initiation of infection is impacted by a heterochromatic-euchromatic dynamic.
- Targeting required epigenetic enzymes suppresses HSV infection and reactivation.

Upon infection, the genomes of herpesviruses undergo a striking transition from a non-nucleosomal structure to a chromatin structure. The rapid assembly and modulation of nucleosomes during the initial stage of infection results in an overlay of complex regulation that requires interactions of a plethora of chromatin modulation components.For herpes simplex virus, the initial chromatin dynamic is dependent on viral and host cell transcription factors and coactivators that mediate the balance between heterochromatic suppression of the viral genome and the euchromatin transition that allows and promotes the expression of viral immediate early genes.Strikingly similar to lytic infection, in sensory neurons this dynamic transition between heterochromatin and euchromatin governs the establishment, maintenance, and reactivation from the latent state. Chromatin dynamics in both the lytic infection and latency-reactivation cycles provides opportunities to shift the balance using small molecule epigenetic modulators to suppress viral infection, shedding, and reactivation from latency.