Previous Article | Next Article 
J Virol. 1994 April; 68(4): 2239-2252
A novel latency-active promoter is contained within the herpes simplex virus type 1 UL flanking repeats.
W F Goins,
L R Sternberg,
K D Croen,
P R Krause,
R L Hendricks,
D J Fink,
S E Straus,
M Levine and
J C Glorioso
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261.
ABSTRACT
Herpes simplex virus type 1 (HSV-1) expresses a unique series of RNA molecules, the latency-associated transcripts or LATs, during latent infection of neuronal tissues. Previous studies by others have described a TATA box-containing latency-active promoter, referred to here as LAP1, located approximately 700 bp upstream of the 5' end of the major 2.0-kb LAT. In this report, transient gene expression assays were employed to identify a second, novel latency-active promoter (LAP2) present within a region downstream of LAP1 and 5' proximal to the major 2.0-kb LAT. In contrast to LAP1, this promoter lacks a TATA box but possesses cis-acting regulatory elements and other features frequently observed within eukaryotic housekeeping gene promoters. Unlike most other HSV promoters, LAP2 was down-regulated by the viral transcriptional activators ICP4 and ICP0. The majority of LAP2-positive regulatory elements were located within sequences from -257 to -58 relative to the 5' end of the 2.0-kb LAT, and the basal promoter mapped within sequences from -14 to +28. RNase protection experiments demonstrated that chimeric LAT-chloramphenicol acetyltransferase transcripts produced in the transient assays initiated at or near the 5' end of the major 2-kb LAT. Tn5 insertional mutagenesis of the ICP4 regulatory gene determined that down-regulation of LAP2 required the ICP4 transactivating domain and targeted the minimal promoter region as the site of action by ICP4. Replicating recombinant viruses containing a LAP2-lacZ reporter gene cassette in an ectopic site (glycoprotein C locus) were shown to be active in mouse trigeminal ganglia. Taken together, these experiments suggest that the LAT region of the HSV-1 genome contains at least two latency-active promoters which may play different roles in expressing the various LATs. Alternatively, these promoters may comprise a larger promoter-regulatory complex which may influence transcription during latency.
J Virol. 1994 April; 68(4): 2239-2252
This article has been cited by other articles:
-
Jin, L., Perng, G.-C., Mott, K. R., Osorio, N., Naito, J., Brick, D. J., Carpenter, D., Jones, C., Wechsler, S. L.
(2005). A Herpes Simplex Virus Type 1 Mutant Expressing a Baculovirus Inhibitor of Apoptosis Gene in Place of Latency-Associated Transcript Has a Wild-Type Reactivation Phenotype in the Mouse. J. Virol.
79: 12286-12295
[Abstract]
[Full Text]
-
Kubat, N. J., Amelio, A. L., Giordani, N. V., Bloom, D. C.
(2004). The Herpes Simplex Virus Type 1 Latency-Associated Transcript (LAT) Enhancer/rcr Is Hyperacetylated during Latency Independently of LAT Transcription. J. Virol.
78: 12508-12518
[Abstract]
[Full Text]
-
Sasaki, K., Chancellor, M. B., Goins, W. F., Phelan, M. W., Glorioso, J. C., de Groat, W. C., Yoshimura, N.
(2004). Gene Therapy Using Replication-Defective Herpes Simplex Virus Vectors Expressing Nerve Growth Factor in a Rat Model of Diabetic Cystopathy. Diabetes
53: 2723-2730
[Abstract]
[Full Text]
-
Jiang, C., Wechuck, J. B., Goins, W. F., Krisky, D. M., Wolfe, D., Ataai, M. M., Glorioso, J. C.
(2004). Immobilized Cobalt Affinity Chromatography Provides a Novel, Efficient Method for Herpes Simplex Virus Type 1 Gene Vector Purification. J. Virol.
78: 8994-9006
[Abstract]
[Full Text]
-
O'Neil, J. E., Loutsch, J. M., Aguilar, J. S., Hill, J. M., Wagner, E. K., Bloom, D. C.
(2004). Wide Variations in Herpes Simplex Virus Type 1 Inoculum Dose and Latency-Associated Transcript Expression Phenotype Do Not Alter the Establishment of Latency in the Rabbit Eye Model. J. Virol.
78: 5038-5044
[Abstract]
[Full Text]
-
Chattopadhyay, M., Goss, J., Wolfe, D., Goins, W. C., Huang, S., Glorioso, J. C., Mata, M., Fink, D. J.
(2004). Protective effect of herpes simplex virus-mediated neurotrophin gene transfer in cisplatin neuropathy. Brain
127: 929-939
[Abstract]
[Full Text]
-
Kubat, N. J., Tran, R. K., McAnany, P., Bloom, D. C.
(2004). Specific Histone Tail Modification and Not DNA Methylation Is a Determinant of Herpes Simplex Virus Type 1 Latent Gene Expression. J. Virol.
78: 1139-1149
[Abstract]
[Full Text]
-
Jones, C.
(2003). Herpes Simplex Virus Type 1 and Bovine Herpesvirus 1 Latency. Clin. Microbiol. Rev.
16: 79-95
[Abstract]
[Full Text]
-
Perng, G.-C., Maguen, B., Jin, L., Mott, K. R., Kurylo, J., BenMohamed, L., Yukht, A., Osorio, N., Nesburn, A. B., Henderson, G., Inman, M., Jones, C., Wechsler, S. L.
(2002). A Novel Herpes Simplex Virus Type 1 Transcript (AL-RNA) Antisense to the 5' End of the Latency-Associated Transcript Produces a Protein in Infected Rabbits. J. Virol.
76: 8003-8010
[Abstract]
[Full Text]
-
Goss, J. R., Goins, W. F., Lacomis, D., Mata, M., Glorioso, J. C., Fink, D. J.
(2002). Herpes Simplex-Mediated Gene Transfer of Nerve Growth Factor Protects Against Peripheral Neuropathy in Streptozotocin-Induced Diabetes in the Mouse. Diabetes
51: 2227-2232
[Abstract]
[Full Text]
-
Perng, G.-C., Maguen, B., Jin, L., Mott, K. R., Osorio, N., Slanina, S. M., Yukht, A., Ghiasi, H., Nesburn, A. B., Inman, M., Henderson, G., Jones, C., Wechsler, S. L.
(2002). A Gene Capable of Blocking Apoptosis Can Substitute for the Herpes Simplex Virus Type 1 Latency-Associated Transcript Gene and Restore Wild-Type Reactivation Levels. J. Virol.
76: 1224-1235
[Abstract]
[Full Text]
-
Ahmed, M., Lock, M., Miller, C. G., Fraser, N. W.
(2002). Regions of the Herpes Simplex Virus Type 1 Latency-Associated Transcript That Protect Cells from Apoptosis In Vitro and Protect Neuronal Cells In Vivo. J. Virol.
76: 717-729
[Abstract]
[Full Text]
-
Burton, E. A., Wechuck, J. B., Wendell, S. K., Goins, W. F., Fink, D. J., Glorioso, J. C.
(2001). Multiple Applications For Replication-Defective Herpes Simplex Virus Vectors. Stem Cells
19: 358-377
[Abstract]
[Full Text]
-
Lilley, C. E., Groutsi, F., Han, Z., Palmer, J. A., Anderson, P. N., Latchman, D. S., Coffin, R. S.
(2001). Multiple Immediate-Early Gene-Deficient Herpes Simplex Virus Vectors Allowing Efficient Gene Delivery to Neurons in Culture and Widespread Gene Delivery to the Central Nervous System In Vivo. J. Virol.
75: 4343-4356
[Abstract]
[Full Text]
-
Berthomme, H., Thomas, J., Texier, P., Epstein, A., Feldman, L. T.
(2001). Enhancer and Long-Term Expression Functions of Herpes Simplex Virus Type 1 Latency-Associated Promoter Are both Located in the Same Region. J. Virol.
75: 4386-4393
[Abstract]
[Full Text]
-
Lock, M., Miller, C., Fraser, N. W.
(2001). Analysis of Protein Expression from within the Region Encoding the 2.0-Kilobase Latency-Associated Transcript of Herpes Simplex Virus Type 1. J. Virol.
75: 3413-3426
[Abstract]
[Full Text]
-
Palmer, J. A., Branston, R. H., Lilley, C. E., Robinson, M. J., Groutsi, F., Smith, J., Latchman, D. S., Coffin, R. S.
(2000). Development and Optimization of Herpes Simplex Virus Vectors for Multiple Long-Term Gene Delivery to the Peripheral Nervous System. J. Virol.
74: 5604-5618
[Abstract]
[Full Text]
-
Berthomme, H., Lokensgard, J., Yang, L., Margolis, T., Feldman, L. T.
(2000). Evidence for a Bidirectional Element Located Downstream from the Herpes Simplex Virus Type 1 Latency-Associated Promoter That Increases Its Activity during Latency. J. Virol.
74: 3613-3622
[Abstract]
[Full Text]
-
Anderson, D. B., Laquerre, S., Goins, W. F., Cohen, J. B., Glorioso, J. C.
(2000). Pseudotyping of Glycoprotein D-Deficient Herpes Simplex Virus Type 1 with Vesicular Stomatitis Virus Glycoprotein G Enables Mutant Virus Attachment and Entry. J. Virol.
74: 2481-2487
[Abstract]
[Full Text]
-
Thomas, S. K., Gough, G., Latchman, D. S., R. S. , , Coffin,
(1999). Herpes Simplex Virus Latency-Associated Transcript Encodes a Protein Which Greatly Enhances Virus Growth, Can Compensate for Deficiencies in Immediate-Early Gene Expression, and Is Likely To Function during Reactivation from Virus Latency. J. Virol.
73: 6618-6625
[Abstract]
[Full Text]
-
Alvira, M. R., Goins, W. F., Cohen, J. B., Glorioso, J. C.
(1999). Genetic Studies Exposing the Splicing Events Involved in Herpes Simplex Virus Type 1 Latency-Associated Transcript Production during Lytic and Latent Infection. J. Virol.
73: 3866-3876
[Abstract]
[Full Text]
-
Goins, W. F., Lee, K. A., Cavalcoli, J. D., O'Malley, M. E., DeKosky, S. T., Fink, D. J., Glorioso, J. C.
(1999). Herpes Simplex Virus Type 1 Vector-Mediated Expression of Nerve Growth Factor Protects Dorsal Root Ganglion Neurons from Peroxide Toxicity. J. Virol.
73: 519-532
[Abstract]
[Full Text]
-
Mador, N., Goldenberg, D., Cohen, O., Panet, A., Steiner, I.
(1998). Herpes Simplex Virus Type 1 Latency-Associated Transcripts Suppress Viral Replication and Reduce Immediate-Early Gene mRNA Levels in a Neuronal Cell Line. J. Virol.
72: 5067-5075
[Abstract]
[Full Text]
-
Arthur, J., Everett, R, Brierley, I, Efstathiou, S
(1998). Disruption of the 5' and 3' splice sites flanking the major latency- associated transcripts of herpes simplex virus type 1: evidence for alternate splicing in lytic and latent infections. J. Gen. Virol.
79: 107-116
[Abstract]
-
Shaw, P., Knez, J., Capone, J. P.
(1995). Amino Acid Substitutions in the Herpes Simplex Virus Transactivator VP16 Uncouple Direct Protein-Protein Interaction and DNA Binding from Complex Assembly and Transactivation. J. Biol. Chem.
270: 29030-29037
[Abstract]
[Full Text]
Copyright © 1994 by the American Society for Microbiology. All rights reserved.