THE COMPARATIVE BIOLOGY OF LATENT HERPES-SIMPLEX VIRUS TYPE-1 AND TYPE-2 INFECTIONS - LATENCY-ASSOCIATED TRANSCRIPT PROMOTER ACTIVITY AND EXPRESSION IN-VITRO AND IN INFECTED MICE

HSV-1 and HSV-2 express abundant latency-associated transcripts (LATs) without which these viruses reactivate in animals inefficiently. To f urther characterize the importance of LATs to the comparative biology of latent HSV-1 and -2 infections, we assessed the relative activities of the viral LAT promoters in vitro using transient transfection assa ys? and the accumulation of LATs in vivo using a mouse ocular infectio n model. In vitro, the HSV-2 LAT promoter proved to be six to tenfold more potent than the HSV-1 promoter in driving reporter gene expressio n. In mice HSV-1 and -2 achieved comparable levels of virus replicatio n in the eye, but HSV-2, grew to higher titers than HSV-1 in trigemina l ganglia and brain. Quantitative-competitive DNA and RNA (RT) PCR and in situ hybridization showed that ganglia latently infected with HSV- 2 contained sixfold more copies of DNA (P=0.003), eightfold more LATS (P=0.01), and ninefold more LAT in situ-positive neurons. However, the numbers of LATs per latent genome were equivalent for both viruses. A lthough the HSV-2 LAT promoter is more potent than the HSV-1 promoter in transient expression assays, the accumulation of HSV-1 and 2 LATs i n mouse trigeminal ganglia is comparable.