Common Strategies Governing Temperate Phage and α-Herpesvirus Persistence

All life-forms can be infected by viruses with double-stranded DNA genomes. Typically, permissive cells support a productive infection, where virus gene expression and DNA replication yield virion progeny resulting in cell death and/or immune clearance. Alternatively, certain viruses, including prokaryotic temperate bacteriophage and herpesviruses that infect multicellular eukaryotes, establish a persistent state in permissive cells (lysogeny in bacteria, latency in eukaryotes) where productive infection is repressed, permitting viral genome maintenance while deferring virus replication and particle assembly until conditions shift to favor productive infection. We compare examples drawn from temperate bacteriophage with more recent developments using the prototypical human α-herpesvirus herpes simplex virus 1 to illustrate mechanisms that control persistence or foster productive infection. Remarkably, despite vast evolutionary distance, similar physiological cues (genome integrity, nutrient status, cell communication signals) govern the switch between persistence and productive infection. Thus, monitoring basic homeostatic indicators determines lysogenic/latent or productive infection outcomes, representing a conserved virus persistence strategy.