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Journal of Virology, December 2007, p. 12962-12972, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.01442-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Recombinant Herpes Simplex Virus Type 1 Expressing Two Additional Copies of gK Is More Pathogenic than Wild-Type Virus in Two Different Strains of Mice

Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Burns & Allen Research Institute, CSMC-D2024, 8700 Beverly Blvd., Los Angeles, California 90048,¹ Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322,² Division of Biotechnology and Molecular Medicine, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803³

Received 2 July 2007/ Accepted 19 September 2007

The effect of glycoprotein K (gK) overexpression on herpes simplex virus type 1 (HSV-1) infection in two different strains of mice was evaluated using a recombinant HSV-1 virus that expresses two additional copies of the gK gene in place of the latency-associated transcript (LAT). This mutant virus (HSV-gK³) expressed higher levels of gK than either the wild-type McKrae virus or the parental dLAT2903 virus both in vitro (in cultured cells) and in vivo (in infected mouse corneas and trigeminal ganglia [TG] of BALB/c and C57BL/6 mice). gK transcripts were detected in the TG of both HSV-gK³-infected mouse strains on day 30 postinfection (p.i.), while gB transcripts were detected only in the TG of the HSV-gK³-infected C57BL/6 mice, a finding that suggests that increased gK levels promote chronic infection. C57BL/6 mice infected with HSV-gK³ also contained free virus in their TG on day 30 p.i. Both HSV-gK³-infected mouse strains had significantly higher corneal scarring (CS) than did McKrae-infected mice. T-cell depletion studies in C57BL/6 mice suggested that this CS enhancement in the HSV-gK³-infected mice was mediated by a CD8⁺ T-cell response. Taken together, these results strongly suggest that increased gK levels promote eye disease and chronic infection in infected mice.

Published ahead of print on 26 September 2007.