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Journal of Virology, October 2001, p. 9018-9028, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9018-9028.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Three Herpes Simplex Virus Type 1 Latency-Associated Transcript Mutants with Distinct and Asymmetric Effects on Virulence in Mice Compared with Rabbits

Guey-Chuen Perng,1 Daniel Esmaili,1 Susan M. Slanina,1 Ada Yukht,1 Homayon Ghiasi,1,2 Nelson Osorio,1 Kevin R. Mott,1 Barak Maguen,1 Ling Jin,1 Anthony B. Nesburn,1,2 and Steven L. Wechsler1,2,*

Ophthalmology Research Laboratories, Cedars-Sinai Medical Center Burns & Allen Research Institute, Los Angeles, California 90048,1 and Department of Ophthalmology, UCLA School of Medicine, Los Angeles, California 900242

Received 9 April 2001/Accepted 14 June 2001

Herpes simplex virus type 1 latency-associated transcript (LAT)-null mutants have decreased reactivation but normal virulence in rabbits and mice. We report here on dLAT1.5, a mutant with LAT nucleotides 76 to 1667 deleted. Following ocular infection of rabbits, dLAT1.5 reactivated at a lower rate than its wild-type parent McKrae (6.1 versus 11.8%; P = 0.0025 [chi-square test]). Reactivation was restored in the marker-rescued virus dLAT1.5R (12.6%; P = 0.53 versus wild type), confirming the importance of the deleted region in spontaneous reactivation. Compared with wild-type or marker-rescued virus, dLAT1.5 had similar or slightly reduced virulence in rabbits (based on survival following ocular infection). In contrast, in mice, dLAT1.5 had increased virulence (P < 0.0001). Thus, deletion of LAT nucleotides 76 to 1667 increased viral virulence in mice but not in rabbits. In contrast, we also report here that LAT2.9A, a LAT mutant that we previously reported to have increased virulence in rabbits (G. C. Perng, S. M. Slanina, A. Yuhkt, B. S. Drolet, W. J. Keleher, H. Ghiasi, A. B. Nesburn, and S. L. Wechsler, J. Virol. 73:920-929, 1999), had decreased virulence in mice (P = 0.03). In addition, we also found that dLAT371, a LAT mutant that we previously reported to have wild-type virulence in rabbits (G. C. Perng, S. M. Slanina, H. Ghiasi, A. B. Nesburn, and S. L. Wechsler, J. Virol. 70:2014-2018, 1996), had decreased virulence in mice (P < 0.05). Thus, these three mutants, each of which encodes a different LAT RNA, have different virulence phenotypes. dLAT1.5 had wild-type virulence in rabbits but increased virulence in mice. In contrast, LAT2.9A had increased virulence in rabbits but decreased virulence in mice, and dLAT371 had wild-type virulence in rabbits but decreased virulence in mice. Taken together, these results suggest that (i) the 5' end of LAT and/or a gene that overlaps part of this region is involved in viral virulence, (ii) this virulence appears to have species-specific effects, and (iii) regulation of this virulence may be complex.

* Corresponding author. Mailing address: Ophthalmology Research Laboratories, Cedars-Sinai Medical Center Burns & Allen Research Institute, Davis Bldg., Room 5072, 8700 Beverly Blvd., Los Angeles, CA 90048. Phone: (310) 423-6457. Fax: (310) 423-0225. E-mail: Wechsler{at}csmc.edu.

Journal of Virology, October 2001, p. 9018-9028, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9018-9028.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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