Molecular circuitry regulating herpes simplex virus type 1 latency in neurons.

Abstract

Herpes simplex virus (HSV) type 1 (HSV-1) enters nerve endings during a primary infection, is transported to sensory ganglia, and establishes latency within nuclei of a subpopulation of neurons. The latent state is characterized by absence of detectable HSV-1 antigen, minimal transcription of productive cycle genes, and high expression of 1.5- and 2-kb viral transcripts, termed the major latency-associated transcripts (LATs), within nuclei of a subpopulation of infected neurons. Transcription within the HSV-1 LAT genomic locus has been reported to both facilitate the establishment of latency in additional neurons and to increase the frequency of spontaneous and induced viral reactivation in animal model systems. More recent evidence suggests some possible mechanisms that may explain the relationship between LATs and both reactivation and establishment of latency. This review summarizes general aspects of latency, but focuses on the structure, expression, and function of LATs, and the interaction between host transcriptional regulators and viral gene expression that may impact latency and reactivation. A model that incorporates evidence from a number of experimental studies is proposed that summarizes the involvement of the LAT locus in the biology of HSV-1 latency.