The comparative biology of latent herpes simplex virus type 1 and type 2 infections: latency-associated transcript promoter activity and expression in vitro and in infected mice.
HSV-1 and HSV-2 express abundant latency-associated transcripts (LATs) without which these viruses reactivate in animals inefficiently. To further characterize the importance of LATs to the comparative biology of latent HSV-1 and -2 infections, we assessed the relative activities of the viral LAT promoters in vitro using transient transfection assays, and the accumulation of LATs in vivo using a mouse ocular infection model. In vitro, the HSV-2 LAT promoter proved to be six to tenfold more potent than the HSV-1 promoter in driving reporter gene expression. In mice HSV-1 and -2 achieved comparable levels of virus replication in the eye, but HSV-2 grew to higher titers than HSV-1 in trigeminal ganglia and brain. Quantitative-competitive DNA and RNA (RT) PCR and in situ hybridization showed that ganglia latently infected with HSV-2 contained sixfold more copies of DNA (P=0.003), eightfold more LATS (P=0.01), and ninefold more LAT in situ-positive neurons. However, the numbers of LATs per latent genome were equivalent for both viruses. Although the HSV-2 LAT promoter is more potent than the HSV-1 promoter in transient expression assays, the accumulation of HSV-1 and 2 LATs in mouse trigeminal ganglia is comparable.
Lekstrom-Himes
J A
JA
Medical Virology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1888, USA.
Wang
K
K
Pesnicak
L
L
Krause
P R
PR
Straus
S E
SE
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004279:DNA, Viral; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008809:Mice, Inbred C3H; D008967:Molecular Biology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology*; D051381:Rats; D014709:Vero Cells; D017735:Virus Latency / Q000502:physiology*
D004279:DNA, Viral