Neuronal Stress Pathway Mediating a Histone Methyl/Phospho Switch Is Required for Herpes Simplex Virus Reactivation

摘要: Herpes simplex virus (HSV) reactivation from latent neuronal infection requires stimulation of lytic gene expression promoters associated with repressive heterochromatin. Various stresses trigger reactivation, but how these stimuli activate silenced remains unknown. We show that a pathway involving activation c-Jun N-terminal kinase (JNK), common to many stress responses, is essential for initial HSV during reactivation. This JNK in neurons mediated by dual leucine zipper (DLK) and JNK-interacting protein 3 (JIP3), which direct toward responses instead other cellular functions. Surprisingly, JNK-mediated viral induction occurs independently histone demethylases remove lysine modifications. Rather, signaling results methyl/phospho switch on promoters, mechanism permitting the presence methylation. present thereby linking neuronal-specific latency.