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Originally published as JGV in Press, 10.1099/vir.0.013318-0 on July 1, 2009 J Gen Virol 90 (2009), 2342-2352; DOI 10.1099/vir.0.013318-0

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Identification of a novel herpes simplex virus type 1 transcript and protein (AL3) expressed during latency

Tareq Jaber1, Gail Henderson2, Sumin Li2, Guey-Chuen Perng3, Dale Carpenter4, Steven L. Wechsler4,5,6 and Clinton Jones1,2

1 School of Biological Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68503, USA
2 Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68503, USA
3 Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA
4 The Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697-4375, USA
5 Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA 92697, USA
6 Center for Virus Research, University of California Irvine, Irvine, CA 92697, USA

Correspondence
Clinton Jones
cjones{at}unlnotes.unl.edu

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is abundantly expressed in latently infected sensory neurons. In small animal models of infection, expression of the first 1.5 kb of LAT coding sequences is necessary and sufficient for wild-type reactivation from latency. The ability of LAT to inhibit apoptosis is important for reactivation from latency. Within the first 1.5 kb of LAT coding sequences and LAT promoter sequences, additional transcripts have been identified. For example, the anti-sense to LAT transcript (AL) is expressed in the opposite direction to LAT from the 5' end of LAT and LAT promoter sequences. In addition, the upstream of LAT (UOL) transcript is expressed in the LAT direction from sequences in the LAT promoter. Further examination of the first 1.5 kb of LAT coding sequences revealed two small ORFs that are anti-sense with respect to LAT (AL2 and AL3). A transcript spanning AL3 was detected in productively infected cells, mouse neuroblastoma cells stably expressing LAT and trigeminal ganglia (TG) of latently infected mice. Peptide-specific IgG directed against AL3 specifically recognized a protein migrating near 15 kDa in cells stably transfected with LAT, mouse neuroblastoma cells transfected with a plasmid containing the AL3 ORF and TG of latently infected mice. The inability to detect the AL3 protein during productive infection may have been because the 5' terminus of the AL3 transcript was downstream of the first in-frame methionine of the AL3 ORF during productive infection.

A supplementary table, listing AL3 primers used in this study, is available with the online version of this paper.







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