Molecular Biology of Herpes Simplex Virus Latency

Abstract

Herpes simplex virus (HSV) has the ability to produce a latent as well as a productive infection in its host. The virus replicates initially in epithelial cells at the site of infection and then spreads by retrograde axonal transport to the sensory ganglia that innervate the infected dermatomes [1,2]. It establishes a productive infection in these ganglia, but this subsides after a few days. The latent infection then ensues, characterized by the asymptomatic persistence of the viral genome in neurons of the trigeminal and sensory dorsal root ganglia [2–7] and, to a lesser extent, of the autonomic and central nervous systems of humans and experimentally inoculated animals [2,8,9]. For reasons as yet poorly understood, the virus may sporadically reactivate and cause a recurrence at or in the neighborhood of the primary site of infection. The immune system plays a critical role in controlling and eliminating both primary and recurrent infections at epithelial surfaces, as well as perhaps clearing subclinical ganglionic reactivations. However, the demonstration that latency can persist in the absence of neutralizing antibodies [10] suggests that molecular factors operating within the infected neuron may be major regulators of latency. This brief review will describe what is known about the molecular biology of the latent HSV infection, and how this information may already suggest possible regulatory mechanisms.