Identical 371-base-pair deletion mutations in the LAT genes of herpes simplex virus type 1 McKrae and 17syn+ result in different in vivo reactivationphenotypes

The herpes simplex virus type 1 (HSV-1) LAT gene is the only viral gene abu ndantly transcribed during latency. WT null mutants created with strains Mc Krae and 17syn+ are impaired for both in vivo spontaneous and in vivo-induc ed reactivation. Thus, LAT is essential for efficient in vivo-induced and s pontaneous reactivation. Different investigators have studied two LAT mutan ts containing a StyI-StyI region deletion corresponding to LAT nucleotides 76 to 447, One mutant, dLAT371 (parent strain, McKrae), had parental high f requencies of spontaneous reactivation. In vivo induced reactivation was no t examined. The other mutant, 17 Delta Sty (parent strain, 17syn+), had par ental frequencies of in vitro reactivation following cocultivation of expla nted ganglia but reduced frequencies of in vivo induced reactivation. Spont aneous reactivation frequency was not reported for 17 Delta Sty, These comb ined results suggested the possibility that in vivo spontaneous reactivatio n and in vivo-induced reactivation may map to different regions within the LAT domain. We now report that dLAT371 has in vivo-induced reactivation fre quencies of the parent and that 17 Delta Sty has reduced frequencies of in vivo spontaneous reactivation. Thus, dLAT371 demonstrated the parental phen otype for both in vivo spontaneous and -induced reactivation while the appa rently identical 17 Delta Sty was impaired for both in vivo spontaneous and -induced reactivation. These results suggest that one or more differences between the genetic backgrounds of McKrae and 17syn+ result in different in vivo reactivation phenotypes of otherwise identical deletion mutations and that McKrae may have compensating sequences sufficient to overcome the los s of the StyI-StyI region of the LAT transcript.