Latent versus productive infection: the alpha herpesvirus switch

Alpha herpesviruses are common pathogens of mammals. They establish a productive infection in many cell types, but a life-long latent infection occurs in PNS neurons. A vast majority of the human population has latent HSV-1 infections. Currently, there is no cure to clear latent infections. Even though HSV-1 is among the best studied viral pathogens, regulation of latency and reactivation is not well understood due to several challenges including a lack of animal models that precisely recapitulate latency/reactivation episodes; a difficulty in modeling in vitro latency; and a limited understanding of neuronal biology. In this review, we discuss insights gained from in vitro latency models with a focus on the neuronal and viral factors that determine the mode of infection.