|
|
||||||||

1 Department of Ophthalmology and Visual Sciences
2 Department of Pathology
and3 Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, U.S.A.
Transient expression assays in PC12 cells showed that the cAMP response element (CRE) and the TATA box of the herpes simplex virus type 1 latency-associated transcripts (LATs) promoter are essential for basal expression. Recombinant viruses were generated containing site-specific mutations in these motifs. The abilities of these recombinants to replicate, express LATs and reactivate from latency were compared with wild-type and marker-rescued viruses in a murine ocular model. The acute replication of these TATA and CRE mutant viruses was at a level equivalent to their respective marker-rescued viruses. The reactivation of virus was unaffected by mutation in the TATA box as compared with wild-type or marker-rescued viruses. In situ hybridization of TATA box mutant virus-infected ganglia, however, showed threefold fewer LAT-positive neurons than wild-type virus-infected ganglia, with consistently weaker hybridization signals. Thus, this TATA box is required for normal expression of the LATs but not for efficient reactivation. The LATs CRE mutant reactivated with slightly but reproducibly reduced frequency and delayed kinetics relative to marker-rescued virus. By in situ hybridization, however, the percentage and intensity of LATs-positive neurons were found to be comparable for the CRE mutant- and wild-type virus-infected ganglia, suggesting that the CRE is dispensable for abundant LATs expression but that a reactivation function of the LATs may depend upon the presence of the CRE. Finally, using a modified assay for examining the timing of reactivation, we showed that the induction of viral reactivation by addition of exogenous cAMP can occur independently of the LATs.
Present address: Program in Biomedical Sciences, University of California San Diego, La Jolla, California 92037, U.S.A.
Received 15 March 1993;
accepted 6 May 1993.
This article has been cited by other articles:
![]() |
T. J. Pasieka, B. Lu, and D. A. Leib Enhanced Pathogenesis of an Attenuated Herpes Simplex Virus for Mice Lacking Stat1 J. Virol., June 15, 2008; 82(12): 6052 - 6055. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. J. Pasieka, B. Lu, S. D. Crosby, K. M. Wylie, L. A. Morrison, D. E. Alexander, V. D. Menachery, and D. A. Leib Herpes Simplex Virus Virion Host Shutoff Attenuates Establishment of the Antiviral State J. Virol., June 1, 2008; 82(11): 5527 - 5535. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. E. Alexander, S. L. Ward, N. Mizushima, B. Levine, and D. A. Leib Analysis of the Role of Autophagy in Replication of Herpes Simplex Virus in Cell Culture J. Virol., November 15, 2007; 81(22): 12128 - 12134. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. S. Strand and D. A. Leib Role of the VP16-Binding Domain of vhs in Viral Growth, Host Shutoff Activity, and Pathogenesis J. Virol., December 15, 2004; 78(24): 13562 - 13572. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. M. Stuart, B. Summers, J. E. Morris, L. A. Morrison, and D. A. Leib CD8+ T cells control corneal disease following ocular infection with herpes simplex virus type 1 J. Gen. Virol., July 1, 2004; 85(7): 2055 - 2063. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Bick, J.-W. N. Carroll, G. Gao, S. P. Goff, C. M. Rice, and M. R. MacDonald Expression of the Zinc-Finger Antiviral Protein Inhibits Alphavirus Replication J. Virol., November 1, 2003; 77(21): 11555 - 11562. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. D. Luker, J. L. Prior, J. Song, C. M. Pica, and D. A. Leib Bioluminescence Imaging Reveals Systemic Dissemination of Herpes Simplex Virus Type 1 in the Absence of Interferon Receptors J. Virol., October 15, 2003; 77(20): 11082 - 11093. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. L. Ward, D. Scheuner, J. Poppers, R. J. Kaufman, I. Mohr, and D. A. Leib In Vivo Replication of an ICP34.5 Second-Site Suppressor Mutant following Corneal Infection Correlates with In Vitro Regulation of eIF2{alpha} Phosphorylation J. Virol., April 15, 2003; 77(8): 4626 - 4634. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Jones Herpes Simplex Virus Type 1 and Bovine Herpesvirus 1 Latency Clin. Microbiol. Rev., January 1, 2003; 16(1): 79 - 95. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. D. Luker, J. P. Bardill, J. L. Prior, C. M. Pica, D. Piwnica-Worms, and D. A. Leib Noninvasive Bioluminescence Imaging of Herpes Simplex Virus Type 1 Infection and Therapy in Living Mice J. Virol., October 25, 2002; 76(23): 12149 - 12161. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. C. Summers and D. A. Leib Herpes Simplex Virus Type 1 Origins of DNA Replication Play No Role in the Regulation of Flanking Promoters J. Virol., June 14, 2002; 76(14): 7020 - 7029. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. J. Smith, L. A. Morrison, and D. A. Leib Pathogenesis of Herpes Simplex Virus Type 2 Virion Host Shutoff (vhs) Mutants J. Virol., March 1, 2002; 76(5): 2054 - 2061. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. C. Summers, T. P. Margolis, and D. A. Leib Herpes Simplex Virus Type 1 Corneal Infection Results in Periocular Disease by Zosteriform Spread J. Virol., June 1, 2001; 75(11): 5069 - 5075. [Abstract] [Full Text] |
||||
![]() |
M. A. Colgin, R. L. Smith, and C. L. Wilcox Inducible Cyclic AMP Early Repressor Produces Reactivation of Latent Herpes Simplex Virus Type 1 in Neurons In Vitro J. Virol., March 15, 2001; 75(6): 2912 - 2920. [Abstract] [Full Text] |
||||
![]() |
B. J. Geiss, T. J. Smith, D. A. Leib, and L. A. Morrison Disruption of Virion Host Shutoff Activity Improves the Immunogenicity and Protective Capacity of a Replication-Incompetent Herpes Simplex Virus Type 1 Vaccine Strain J. Virol., December 1, 2000; 74(23): 11137 - 11144. [Abstract] [Full Text] |
||||
![]() |
L. F. van Dyk, H. W. Virgin IV, and S. H. Speck The Murine Gammaherpesvirus 68 v-Cyclin Is a Critical Regulator of Reactivation from Latency J. Virol., August 15, 2000; 74(16): 7451 - 7461. [Abstract] [Full Text] |
||||
![]() |
T. J. Smith, C. E. Ackland-Berglund, and D. A. Leib Herpes Simplex Virus Virion Host Shutoff (vhs) Activity Alters Periocular Disease in Mice J. Virol., April 15, 2000; 74(8): 3598 - 3604. [Abstract] [Full Text] |
||||
![]() |
E. T. Clambey, H. W. Virgin IV, and S. H. Speck Disruption of the Murine Gammaherpesvirus 68 M1 Open Reading Frame Leads to Enhanced Reactivation from Latency J. Virol., February 15, 2000; 74(4): 1973 - 1984. [Abstract] [Full Text] |
||||
![]() |
D. A. Leib, T. E. Harrison, K. M. Laslo, M. A. Machalek, N. J. Moorman, and H. W. Virgin Interferons Regulate the Phenotype of Wild-type and Mutant Herpes Simplex Viruses In Vivo J. Exp. Med., February 15, 1999; 189(4): 663 - 672. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. M. Sawtell, D. K. Poon, C. S. Tansky, and R. L. Thompson The Latent Herpes Simplex Virus Type 1 Genome Copy Number in Individual Neurons Is Virus Strain Specific and Correlates with Reactivation J. Virol., July 1, 1998; 72(7): 5343 - 5350. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. A. Leib, M. A. Machalek, B. R. G. Williams, R. H. Silverman, and H. W. Virgin From the Cover: Specific phenotypic restoration of an attenuated virus by knockout of a host resistance gene PNAS, May 23, 2000; 97(11): 6097 - 6101. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| INT J SYST EVOL MICROBIOL | MICROBIOLOGY | J GEN VIROL |
| J MED MICROBIOL | ALL SGM JOURNALS | |