ACCUMULATION OF VIRAL TRANSCRIPTS AND DNA DURING ESTABLISHMENT OF LATENCY BY HERPES-SIMPLEX VIRUS

Latent infection of mice with wild-type herpes simplex virus is establ ished during an acute phase of ganglionic infection in which there is abundant viral replication and productive-cycle gene expression. Thymi dine kinase-negative mutants establish latent infections but are sever ely impaired for acute ganglionic replication and productive-cycle gen e expression. Indeed, by in situ hybridization assays, acute infection by these mutants resembles latency. To assess events during establish ment of latency by wild-type and thymidine kinase-negative viruses, we quantified specific viral nucleic acid sequences in mouse trigeminal ganglia during acute ganglionic infection by using sensitive PCR-based assays. Through 32 h postinfection, viral DNA and transcripts represe ntative of the three kinetic classes of productive-cycle genes accumul ated to comparable levels in wild-type- and mutant-infected ganglia. A t 48 and 72 h, although latency-associated transcripts accumulated to comparable levels in ganglia infected with wild-type or mutant virus, levels of DNA accumulating in wild-type-infected ganglia exceeded thos e in mutant-infected ganglia by 2 to 3 orders of magnitude. Coincident with this increase in DNA, wild-type-infected ganglia exhibited abund ant expression of productive-cycle genes and high titers of infectious progeny, Nevertheless, the levels of productive-cycle RNAs expressed by mutant virus during acute infection greatly exceeded those expresse d by wild-type virus during latency. The results thus distinguish acut e infection of ganglia by a replication-compromised mutant from latent infection and may have implications for mechanisms of latency.