IMPORTANCE OF THE HERPES-SIMPLEX VIRUS UL24 GENE FOR PRODUCTIVE GANGLIONIC INFECTION IN MICE

The UL24 gene of herpes simplex virus overlaps the viral thymidine kin ase (tk) gene. Most previous studies of UL24 have examined UL24 mutant s that have also contained tk and sometimes other mutations. To addres s the importance of UL24 for viral replication in cell culture and in infections of a mammalian host, we constructed a mutant virus containi ng a UL24 nonsense mutation that does not affect TK activity and a sec ond mutant that contains clustered point mutations in UL24 and a mutat ion in tk that does not by itself affect the ability of the virus to r eplicate acutely in mouse ganglia or to reactivate from latent infecti on following corneal inoculation of mice. Both mutant viruses replicat ed in cells in culture and in the mouse eye, albeit less efficiently t han wild type or control viruses. Both mutants were much more severely impaired for acute replication in trigeminal ganglia and for reactiva tion from latency following explant of these ganglia. Viral DNA and la tency-associated transcripts were present, albeit at lower levels in g anglia infected with the nonsense mutant These results indicate that U L24 is especially important for productive infection of mouse sensory ganglia and may have implications for the behaviors of certain tk muta nts in pathogenesis. (C) 1998 Academic Press.