Herpesviruses use two contrasting infection strategies: productive (or lytic) replication and latency, constituting fundamentally different viral gene expression programs with contrary goals and outcomes. Latency maintains the viral genome for long periods without producing infectious progeny, but allows the virus to re-engage in productive replication, a process known as reactivation. This ensures long-term persistence as well as dissemination to new host cells or organisms. During latency the infected cell is also changed such that its lifespan is extended and the virus is shielded from immune clearance. But how latency works turns out to be very difficult to understand.
A cultured affair: HSV latency and reactivation in neurons. Trends Microbiol. 7 Sep 2012
After replicating in surface epithelia, herpes simplex virus type-1 (HSV-1) enters the axonal terminals of peripheral neurons. The viral genome translocates to the nucleus, where it establishes a specialized infection known as latency, re-emerging periodically to seed new infections. Studies using cultured neuron models that faithfully recapitulate the molecular hallmarks of latency and reactivation defined in live animal models have provided fresh insight into the control of latency and connections to neuronal physiology. With this comes a growing appreciation for how the life cycles of HSV-1 and other herpesviruses are governed by key host pathways controlling metabolic homeostasis and cell identity.
Herpesvirus transport to the nervous system and back again. (2012) Annu Rev Microbiol. 66: 153-76
Herpes simplex virus, varicella zoster virus, and pseudorabies virus are neurotropic pathogens of the Alphaherpesvirinae subfamily of the Herpesviridae. These viruses efficiently invade the peripheral nervous system and establish lifelong latency in neurons resident in peripheral ganglia. Primary and recurrent infections cycle virus particles between neurons and the peripheral tissues they innervate. This remarkable cycle of infection is the topic of this review. In addition, some of the distinguishing hallmarks of the infections caused by these viruses are evaluated in terms of their underlying similarities.