EVIDENCE FOR A NOVEL REGULATORY PATHWAY FOR HERPES-SIMPLEX VIRUS GENE-EXPRESSION IN TRIGEMINAL GANGLION NEURONS

Thymidine kinase (TK)-negative (TK-) mutant strains of herpes simplex virus type 1 (HSV-1) show reduced expression of alpha and beta viral g enes during acute infection of trigeminal ganglion neurons following c orneal infection (M. Kosz-Vnenchak, D. M. Coen, and D. M. Knipe, J. Vi rol. 64:5396-5402, 1990). It was surprising that a defect in a beta ge ne product would lead to decreased alpha and beta gene expression, giv en the regulatory pathways demonstrated for HSV infection of cultured cells. In this study, we have examined viral gene expression during re activation from latent infection in explanted trigeminal ganglion tiss ue. In explant reactivation studies with wild-type virus, we observed viral productive gene expression over the first 48 h of explant incuba tion occurring in a temporal order (alpha beta, gamma) similar to that in cultured cells. This occurred predominantly in latency-associated transcript-positive neurons but was limited to a fraction of these cel ls. In contrast, TK- mutant viruses showed greatly reduced alpha and b eta gene expression upon explant of latently infected trigeminal gangl ion tissue. An inhibitor of viral TK or an inhibitor of viral DNA poly merase greatly decreased viral lytic gene expression in trigeminal gan glion tissue latently infected with wild-type virus and explanted in c ulture. These results indicate that the regulatory mechanisms governin g HSV gene expression are different in trigeminal ganglion neurons and cultured cells. We present a new model for viral gene expression in t rigeminal ganglion neurons with implications for the nature of the dec ision process between latent infection and productive infection by HSV .