Ongoing studies in mice with a recombinant vaccinia virus vaccine for herpes simplex (HSV) have shown that substantial but somewhat reduced protection against both lethal and latent infection with HSV-1 persists for greater than one year post vaccination with a single vaccination of the vaccinia-herpes recombinant. Mice boosted with a second vaccination of the recombinant demonstrated increased neutralizing antibody to HSV and increased protection against lethal infection with HSV-1. We have developed a manipulable model of ultraviolet (UV) light-induced reactivation of HSV in humans. Using this model, we have initiated a double blinded protocol to investigate the ability of the antiviral agent acyclovir to block UV induced reactivation of HSV in patients with frequently recurrent nongenital HSV. One of the major open questions in the molecular biology of HSV latency is the identification of viral genes responsible for maintenance of the latent state of HSV in host ganglia. Using c-DNA probes made from trigeminal ganglia RNA of mice latently infected with HSV we have identified a viral gene or subset of genes which appear to be transcribed throughout the latent phase of infection. This gene(s) maps in the UL region of the UL-IRP boundary of the viral genome. Impairment of enzyme clearance may be a more important factor than previously suspected in regulating enzyme levels in disease states. Studies in mice conducted over the past year have shown that alteration of the function of the reticuloendothelial system whether due to environmental or genetic causes yields changes in the clearance of the enzyme lactic dehydrogenase (LDH) and consequent changes in serum levels of LDH.
