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Journal of Virology, April 2001, p. 3636-3646, Vol. 75, No. 8
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.8.3636-3646.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Region of Herpes Simplex Virus Type 1 Latency-Associated Transcript Sufficient for Wild-Type Spontaneous
Reactivation Promotes Cell Survival in Tissue Culture
Melissa
Inman,1
Guey-Chuen
Perng,2
Gail
Henderson,1
Homayon
Ghiasi,2,3
Anthony B.
Nesburn,2,3
Steven L.
Wechsler,2,3 and
Clinton
Jones1,*
Department of Veterinary and Biomedical
Sciences, University of Nebraska, Lincoln, Nebraska
68583-09051; Ophthalmology Research
Laboratories, Cedars-Sinai Medical Center Burns & Allen Research
Institute, Los Angeles, California 900482; and
Department of Ophthalmology, UCLA School of Medicine, Los
Angeles, California 900243
Received 16 October 2000/Accepted 24 January 2001
The latency-associated transcript (LAT) is the only abundant herpes
simplex virus type 1 (HSV-1) transcript expressed during latency. In
the rabbit eye model, LAT null mutants do not reactivate efficiently
from latency. We recently demonstrated that the LAT null mutant
dLAT2903 induces increased levels of apoptosis in trigeminal ganglia of infected rabbits compared to LAT+
strains (G.-C. Perng, C. Jones, J. Ciacci-Zarella, M. Stone, G. Henderson, A. Yokht, S. M. Slanina, F. M. Hoffman, H. Ghiasi, A. B. Nesburn, and C. S. Wechsler, Science 287:1500-1503,
2000).The same study also demonstrated that a plasmid expressing LAT
nucleotides 301 to 2659 enhanced cell survival of transfected cells
after induction of apoptosis. Consequently, we hypothesized that LAT enhances spontaneous reactivation in part, because it promotes survival
of infected neurons. Here we report on the ability of plasmids
expressing different portions of the 5' end of LAT to promote cell
survival after induction of apoptosis. A plasmid expressing the first
1.5 kb of LAT (LAT nucleotides 1 to 1499) promoted cell survival in
neuro-2A (mouse neuronal) and CV-1 (monkey fibroblast) cells. A plasmid
expressing just the first 811 nucleotides of LAT promoted cell survival
less efficiently. Plasmids expressing the first 661 nucleotides or less
of LAT did not promote cell survival. We previously showed that a
mutant expressing just the first 1.5 kb of LAT has wild-type
spontaneous reactivation in rabbits, and a mutant expressing just the
first 811 nucleotides of LAT has a reactivation frequency higher than
that of dLAT2903 but lower than that of wild-type virus. In
addition, mutants reported here for the first time, expressing just the
first 661 or 76 nucleotides of LAT, had spontaneous reactivation
indistinguishable from that of the LAT null mutant
dLAT2903. In summary, these studies provide evidence that
there is a functional relationship between the ability of LAT to
promote cell survival and its ability to enhance spontaneous reactivation.
*
Corresponding author. Mailing address: Dept. of
Veterinary and Biomedical Sciences, University of Nebraska, Lincoln,
Fair Street at East Campus Loop, Lincoln, NE 68583-0905, Phone: (402) 472-1890. Fax: (402) 472-9690. E-mail:
cjones{at}unlnotes.unl.edu.
Journal of Virology, April 2001, p. 3636-3646, Vol. 75, No. 8
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.8.3636-3646.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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