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Journal of Virology, May 2004, p. 5038-5044, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5038-5044.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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. E. O'Neil,1 J. M. Loutsch,2 J. S. Aguilar,3 J. M. Hill,2 E. K. Wagner,3 and D. C. Bloom1*

Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, Florida,1 Louisiana State University Eye Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana,2 Department of Molecular Biology & Biochemistry, University of California, Irvine, California3

Received 18 October 2003/ Accepted 15 January 2004

The latency-associated transcript (LAT) is required for efficient reactivation of herpes simplex virus type 1 from latent infection in the rabbit eye model, but LAT's mechanism of action is unknown. In addition to reactivation, the LAT region seems to correspond to multiple functions, with some LAT deletion mutants exhibiting increased virulence, increased neuronal death, and restricted establishment of latency. While a LAT promoter deletion mutant (17{Delta}Pst) seems to be primarily restricted in reactivation in the rabbit, subtle effects on virulence or the establishment of latency cannot be precluded at the normal high levels of virus inoculum used in the rabbit model. Since such additional LAT phenotypes may be more evident with lower doses of virus, we evaluated the influence of initial viral inoculum and LAT expression on the progression of acute infection and the establishment of latency. We have assayed both virus recovery rates and viral genome loads in rabbit corneas and trigeminal ganglia. Our results show that (i) in the corneas and trigeminal ganglia, the maximum amount of virus present during acute infection is independent of the LAT genotype and inoculum dose, although greater viral yields are obtained earlier with higher inoculum doses, and (ii) the range in numbers of latent genomes detected in the ganglia is independent of the inoculum dose and the LAT genotype and therefore no difference in establishment of latency is observed.


* Corresponding author. Mailing address: Department of Molecular Genetics & Microbiology, Box 100266, University of Florida College of Medicine, Gainesville, FL 32610-0266. Phone: (352) 392-8520. Fax: (352) 392-3133. E-mail: dbloom{at}ufl.edu.


Journal of Virology, May 2004, p. 5038-5044, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5038-5044.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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