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Journal of Virology, October 2001, p. 9029-9036, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9029-9036.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Recombinant Herpes Simplex Virus Type 1 Expressing Murine Interleukin-4 Is Less Virulent than Wild-Type Virus in Mice

Homayon Ghiasi,1,2,* Yanira Osorio,1 Guey-Chuen Perng,1 Anthony B. Nesburn,1,2 and Steven L. Wechsler1,2

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

Received 13 April 2001/Accepted 25 June 2001

The effect of interleukin-4 (IL-4) on herpes simplex virus type 1 (HSV-1) infection in mice was evaluated by construction of a recombinant HSV-1 expressing the gene for murine IL-4 in place of the latency-associated transcript (LAT). The mutant virus (HSV-IL-4) expressed high levels of IL-4 in cultured cells. The replication of HSV-IL-4 in tissue culture and in trigeminal ganglia was similar to that of wild-type virus. In contrast, HSV-IL-4 appeared to replicate less well in mouse eyes and brains. Although BALB/c mice are highly susceptible to HSV-1 infection, ocular infection with HSV-IL-4 resulted in 100% survival. Furthermore, 57% of the mice survived coinfection with a mixture of HSV-IL-4 and a lethal dose of wild-type McKrae, compared with only 10% survival following infection with McKrae alone. Similar to wild-type BALB/c mice, 100% of IL-4-/- mice also survived HSV-IL-4 infection. T-cell depletion studies suggested that protection against HSV-IL-4 infection was mediated by a CD4+-T-cell response.

* Corresponding author. Mailing address: Ophthalmology Research---Davis Bldg. Rm. 5072, Cedars-Sinai Research Institute, 8700 Beverly Blvd., Los Angeles, CA 90048. Phone: (310) 423-0593. Fax: (310) 423-0225. E-mail: ghiasih{at}CSHS.org.

Journal of Virology, October 2001, p. 9029-9036, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.9029-9036.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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