AN HSV-1 CONTAINING THE RAT BETA-GLUCURONIDASE CDNA INSERTED WITHIN THE LAT GENE IS LESS EFFICIENT THAN THE PARENTAL STRAIN AT ESTABLISHINGA TRANSCRIPTIONALLY ACTIVE STATE DURING LATENCY IN NEURONS

The herpes simplex virus vector 17/LAT-RGUSB has previously been shown to express beta-glucuronidase enzyme activity stably in the trigemina l ganglia and brain stems of beta-glucuronidase-deficient mutant mice. (1) However, the number of beta-glucuronidase expressing cells in trig eminal ganglia latently infected with 17/LAT-RGUSB was smaller than ex pected. Using normal mice for further characterization of 17/LAT-RGUSB latent infection, no appreciable differences were found between the v ector and wild-type virus in: (1) their abilities to replicate in acut ely infected ganglia; (2) their abilities to reactivate from latently infected ganglia or (3) the quantities of viral DNA in tissues during the acute or the latent phases of infection. Using a minor LAT (mLAT)- specific probe to detect transcription by in situ hybridization, it wa s found that the intensity of the signal from individual cells latentl y-infected with 17/LAT-RGUSB or wild-type virus was similar. However, the vector-infected ganglia had only 20% as many positive cells as in wild-type infection. These data suggest that 17/LAT-RGUSB virus establ ished latency similarly to wild-type virus, but that the LAT-promoter driven gene expression was compromised.