Abstract
The dynamic nature of interactions between invading viral pathogens and their hosts has fascinated scientists for several decades. The well-known capacity of herpes simplex virus (HSV) to establish life-long infections in humans reflects a dynamic balance between maintaining a latent state in which viral genomes are silenced and re-entry into the lytic phase during reactivation. Silencing of the viral genome has been shown to be a function of innate immune signalling, intrinsic cellular antiviral mechanisms and epigenetic repression. Thus, although many important observations have been made identifying cellular processes that contribute to the repression of the viral genome and latency, the field has lacked an understanding of how these factors work together. In this issue of EMBO Reports, Suzich et al (2021) present convincing evidence that brings together individual observations into a cohesive model that explains many of these outstanding mysteries. Here, we will review the background data that lead to this outstanding piece of work.