Similarities in regulation of the HSV-1 LAT promoter in corneal and neuronal cells.
OBJECTIVE
To address the possibility of neuronal-like herpes simplex virus type 1 (HSV-1) latency in the cornea by determining if regulation of the HSV-1 LAT promoter in stromal keratocytes is similar to LAT promoter regulation in neurons.


METHODS
Transient chloramphenicol acetyltransferase (CAT) assays were used to measure the relative promoter activity of various HSV-1 LAT promoter fragments in primary human corneal cells versus neuronal and nonneuronal cells.


RESULTS
The authors found that the LAT promoter, whose location they previously mapped in neurons using transient CAT assays, functioned in stromal keratocytes using the same assay system and that two regions between -283 and -1932 nucleotides relative (upstream) to the start of LAT transcription slightly increased the LAT promoter activity in stromal keratocytes. They previously showed a similar increase in neuronal cells, and a large decrease in nonneuronal cells. In addition, they found that a neuronal specific enhancer region they previously defined between -162 and -283 nucleotides upstream of the start of LAT transcription also enhanced promoter activity in stromal keratocytes. Using gel-shift assays, they detected a nuclear factor specific to neurons and stromal keratocytes that binds to the LAT promoter and that may be a LAT regulatory factor.


CONCLUSIONS
Recently, it has been suggested that the cornea might serve as an alternative site of latent herpes simplex virus type 1 (HSV-1) infection. However, this remains controversial. The authors' findings suggest that corneal and neuronal cells regulate the LAT promoter similarly and that this regulation differs from that seen in nonneuronal cells. Thus, the possibility of neuronal-like latency in the cornea remains plausible.
Perng
G C
GC
Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Zwaagstra
J C
JC
Ghiasi
H
H
Kaiwar
R
R
Brown
D J
DJ
Nesburn
A B
AB
Wechsler
S L
SL
D000818:Animals; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003319:Corneal Stroma / Q000378:metabolism* / Q000382:microbiology; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000382:microbiology; D011401:Promoter Regions, Genetic; D051381:Rats; D014407:Tumor Cells, Cultured; D017735:Virus Latency / Q000502:physiology
D015500:Chloramphenicol O-Acetyltransferase