The latency-associated transcript gene of herpes simplex virus type 1 (HSV-1) is required for efficient in vivo spontaneous reactivation of HSV-1 from latency.
During herpes simplex virus type 1 (HSV-1) neuronal latency, the only viral RNA detected is from the latency-associated transcript (LAT) gene. We have made a LAT deletion mutant of McKrae, an HSV-1 strain with a very high in vivo spontaneous reactivation rate. This mutant (dLAT2903) lacks the LAT promoter and the first 1.6 kb of the 5' end of LAT. dLAT2903 was compared with its parental virus and with a rescued virus containing a restored LAT gene (dLAT2903R). Replication of the LAT mutant in tissue culture, rabbit eyes, and rabbit trigeminal ganglia was similar to that of the rescued and parental viruses. On the basis of semiquantitative PCR analysis of the amount of HSV-1 DNA in trigeminal ganglia, the LAT mutant was unimpaired in its ability to establish latency. In contrast, spontaneous reactivation of dLAT2903 in the rabbit ocular model of HSV-1 latency and reactivation was decreased to approximately 33% of normal. This decrease was highly significant (P < 0.0001) and demonstrates that in an HSV-1 strain with a high spontaneous reactivation rate, deletion of LAT can dramatically decrease in vivo spontaneous reactivation. We also report here that deletion of LAT appeared to eliminate rather than just reduce in vivo induced reactivation.
Perng
G C
GC
Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Dunkel
E C
EC
Geary
P A
PA
Slanina
S M
SM
Ghiasi
H
H
Kaiwar
R
R
Nesburn
A B
AB
Wechsler
S L
SL
D000818:Animals; D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis / Q000302:isolation & purification; D005123:Eye / Q000821:virology; D005260:Female; D017353:Gene Deletion; D005814:Genes, Viral; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D016849:Keratitis, Herpetic / Q000503:physiopathology* / Q000821:virology; D007668:Kidney; D007700:Kinetics; D009474:Neurons / Q000821:virology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011817:Rabbits; D013045:Species Specificity; D013997:Time Factors; D014158:Transcription, Genetic; D012668:Trigeminal Ganglion / Q000821:virology; D014775:Virus Activation; D017735:Virus Latency / Q000235:genetics*; D014779:Virus Replication
D004279:DNA, Viral