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Herpes simplex virus Research
Animations of steps of HSV Infection and Replication
Latent infection and reactivation by HSV takes place in sensory neurons, primarily in the trigeminal ganglia for HSV-1. The process of establishment involves virus entering neurons at the periphery, and the viral genome traveling up the axon and entering the nucleus. While some neurons are destroyed as virus replicates, most neurons are refractory to virus replication and the viral genomes become associated with host histones and persist as mini-chromosomes.
The expression of most viral genes is absent during latent infection, but a number of latently infected neurons express a single transcript--the latency associated transcript or LAT--which is encoded in the repeat regions of the genome.
LAT expression facilitates reactivation, but its mechanism of action is unclear at this time. It does not appear to directly involve the expression of a protein. A 2 kb intron is spliced from the primary transcript. This intron is stable in the nucleus of the latently infected neuron and persists as a circular "lariat" form, but this stable intron is not required for the facilitation of reactivation mediated by LAT. The spliced, polyadenylated LAT can be detected with difficulty in some latently infected neurons; a region of about 350 bases in the extreme 5' end of this transcript is required for LAT-facilitated reactivation.
Reactivation occurs following physiological stress to the animal. During this event some productive phase transcripts and proteins can be detected in the neuron, and infectious virus appears at the periphery (the site where the virus originally entered). This virus can initiate a general infection at the peripheral site where limited virus replication takes place until the host defense systems respond and suppress it. It is not known whether the reactivation event involves the killing of one or a few neurons, but most evidence suggests that the frequency of reactivation decreases with time.
Illustration and Flash animations by
Scientific, Medical and Veterinary Illustration.
The animations are available for download for classroom teaching.