title: 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.
abstract: The herpes simplex virus type 1 (HSV-1) LAT gene is the only viral gene abundantly transcribed during latency. LAT 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, 17DeltaSty (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 17DeltaSty. 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 17DeltaSty 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 17DeltaSty 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.
authors.affiliation: LSU Eye Center, Department of Ophthalmology, Microbiology and Immunology, and Department of Pharmacology, Louisiana State University Medical Center School of Medicine, New Orleans, Louisiana 70112-2234, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Loutsch
authors.forename: G C
authors.initials: GC
authors.lastname: Perng
authors.forename: J M
authors.initials: JM
authors.lastname: Hill
authors.forename: X
authors.initials: X
authors.lastname: Zheng
authors.forename: M E
authors.initials: ME
authors.lastname: Marquart
authors.forename: T M
authors.initials: TM
authors.lastname: Block
authors.forename: H
authors.initials: H
authors.lastname: Ghiasi
authors.forename: A B
authors.initials: AB
authors.lastname: Nesburn
authors.forename: S L
authors.initials: SL
authors.lastname: Wechsler
mesh_terms: D000818:Animals; D020029:Base Pairing; D005814:Genes, Viral; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology*; D009154:Mutation; D010641:Phenotype; D011817:Rabbits; D014775:Virus Activation; D017735:Virus Latency / Q000235:genetics*