Herpes simplex virus type 1 latency-associated transcription unit promotes anatomical site-dependent establishment and reactivation from latency.
Defined herpes simplex virus type 1 (HSV-1) mutants KOS/1 and KOS/62 (positive and negative, respectively, for latency-associated transcripts [LATs]) express the Escherichia coli beta-galactosidase (beta-Gal) gene during latency. These mutants were employed to assess the functions of the latency-associated transcription unit on establishment and maintenance of and reactivation from the latent state. It was found that in the trigeminal ganglia, the frequencies of hyperthermia-induced reactivation of KOS/62 and an additional LATs- mutant (KOS/29) were reduced by at least 80%. Quantification of latently infected neurons expressing the beta-Gal gene revealed that the LATs- mutant KOS/62 established approximately 80% fewer latent infections in the trigeminal ganglia than did KOS/1 (LATs+). This reduction in establishment which is evident in the trigeminal ganglia could account for the reduced frequency of reactivation from this site. In striking contrast, both LATs- mutants reactivated with wild-type frequencies from lumbosacral ganglia. Quantification of beta-Gal-positive neurons at this site revealed that KOS/62 established as many as or more latent infections than the LATs+ virus, KOS/1. Colocalization of HSV antigen and beta-Gal suggested that the decreased establishment by LATs- mutants in trigeminal ganglia was the result of inefficient viral shutoff. Thus, one function of the HSV-1 LATs transcription unit is to promote the establishment of latency in trigeminal but not lumbosacral ganglia. Such a function may be relevant to understanding the distinct clinical recurrent disease patterns of HSV-1 and HSV-2.
Sawtell
N M
NM
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati Medical Center, Ohio 45267-0524.
Thompson
R L
RL
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D004279:DNA, Viral / Q000302:isolation & purification; D005724:Ganglia / Q000382:microbiology; D006561:Herpes Simplex / Q000382:microbiology; D007700:Kinetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D018139:Simplexvirus / Q000235:genetics* / Q000254:growth & development; D014158:Transcription, Genetic; D014775:Virus Activation; D014779:Virus Replication
D004279:DNA, Viral