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

The herpes simplex virus type 1 (HSV-1) LAT gene is the only viral gene abundantly transcribed during latency. WT null mutants created with strains McKrae and 17syn+ are impaired for both in vivo spontaneous and in vivo-induced reactivation. Thus, LAT is essential for efficient in vivo-induced and spontaneous reactivation. Different investigators have studied two LAT mutants containing a StyI-StyI region deletion corresponding to LAT nucleotides 76 to 447, One mutant, dLAT371 (parent strain, McKrae), had parental high frequencies of spontaneous reactivation. In vivo induced reactivation was not examined. The other mutant, 17 Delta Sty (parent strain, 17syn+), had parental frequencies of in vitro reactivation following cocultivation of explanted ganglia but reduced frequencies of in vivo induced reactivation. Spontaneous reactivation frequency was not reported for 17 Delta Sty, These combined results suggested the possibility that in vivo spontaneous reactivation and in vivo-induced reactivation may map to different regions within the LAT domain. We now report that dLAT371 has in vivo-induced reactivation frequencies of the parent and that 17 Delta Sty has reduced frequencies of in vivo spontaneous reactivation. Thus, dLAT371 demonstrated the parental phenotype for both in vivo spontaneous and -induced reactivation while the apparently 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 loss of the StyI-StyI region of the LAT transcript.