An analysis of herpes simplex virus gene expression during latency establishment and reactivation.

Abstract

In order to facilitate an analysis of the pattern of herpes simplex virus gene expression during latency establishment and reactivation, recombinant viruses containing the lacZ reporter gene under control of either the immediate early 110 (IE110) promoter or the latency-associated promoter have been constructed. Histochemical staining of ganglia taken from mice infected with these viruses allows for the rapid identification and quantification of sensory neurones in which these two promoters are active. Using the mouse ear model, this study demonstrates that, during the establishment of latency in vivo, IE110 promoter activity is only detectable in ganglia which provide innervation to the site of virus inoculation. Latency, however, is efficiently established not only in these ganglia, but also in adjacent ganglia whose neurones do not innervate the ear, and in which there was no evidence of IE110 expression during the acute phase of infection. This implies that replication-competent virus can efficiently establish latency in the absence of detectable IE110 expression. In addition, it has been possible to investigate viral gene expression in neurones following ganglionic explant culture by monitoring IE110 promoter-driven lacZ expression within reactivating neurones. This study shows that virus can be reactivated from all latently infected ganglia, but that reactivation appears to be more efficient from ganglia which provide innervation to the site of infection. The implications of these results for the mechanisms involved in latency establishment and reactivation are discussed.