EXPERIMENTAL INVESTIGATION OF HERPES-SIMPLEX VIRUS LATENCY

The clinical manifestations of herpes simplex virus infection generall y involve a mild and localized primary infection followed by asymtomat ic (latent) infection interrupted sporadically by periods of recrudesc ence (reactivation) where virus replication and associated cytopatholo gic findings are manifest at the site of initial infection. During the latent phase of infection, viral genomes, bur not infectious virus it self; can be detected in sensory and autonomic neurons. The process of latent infection and reactivation has been subject to containing inve stigation in animal models and more recently, in cultured cells. The i nitiation and maintenance of latent infection in neurons are apparentl y passive phenomena in that no virus gene products need be expressed o r are required. Despite this, a single latency-associated transcript ( LAT) encoded by DNA encompassing about 6% of the viral genome is expre ssed during latent infection in a minority of neurons containing viral DNA. This transcript is spliced, and the intron derived from this spl icing is stably maintained in the nucleus of neurons expressing it. Re activation, which can be induced by stress and assayed in several anim al models, is facilitated by the expression of LAT. Although the mecha nism of action of LAT-mediated facilitation of reactivation is not cle ar, all available evidence argues against its involving the expression of a protein. Rather, the most consistent models of action involve LA T expression playing a cis-acting role in a very early stage of the re activation process.