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Journal of Virology, September 2002, p. 9398-9406, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9398-9406.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Antiviral Efficacy of the Murine Alpha-1 Interferon Transgene against Ocular Herpes Simplex Virus Type 1 Requires the Presence of CD4⁺, /ß T-Cell Receptor-Positive T Lymphocytes with the Capacity To Produce Gamma Interferon

Departments of Ophthalmology,¹ Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104²

Received 11 March 2002/ Accepted 20 June 2002

Alpha/beta interferons (IFN-/ßs) are known to antagonize herpes simplex virus type 1 (HSV-1) infection by directly blocking viral replication and promoting additional innate and adaptive, antiviral immune responses. To further define the relationship between the adaptive immune response and IFN-/ß, the protective effect induced following the topical application of plasmid DNA containing the murine IFN-1 transgene onto the corneas of wild-type and T-cell-deficient mice was evaluated. Mice homozygous for both the T-cell receptor (TCR) ß- and -targeted mutations expressing no ß or TCR (ß/ TCR double knockout [dKO]) treated with the IFN-1 transgene succumbed to ocular HSV-1 infection at a rate similar to that of ß/ TCR dKO mice treated with the plasmid vector DNA. Conversely, mice with targeted disruption of the TCR chain and expressing no TCR⁺ cells treated with the IFN-1 transgene survived the infection to a greater extent than the plasmid vector-treated counterpart and at a level similar to that of wild-type controls treated with the IFN-1 transgene. By comparison, mice with targeted disruption of the TCR ß chain and expressing no ß TCR⁺ cells (ß TCR knockout [KO]) showed no difference upon treatment with the IFN-1 transgene or the plasmid vector control, with 0% survival following HSV-1 infection. Adoptively transferring CD4⁺ but not CD8⁺ T cells from wild-type but not IFN--deficient mice reestablished the antiviral efficacy of the IFN-1 transgene in ß TCR KO mice. Collectively, the results indicate that the protective effect mediated by topical application of a plasmid construct containing the murine IFN-1 transgene requires the presence of CD4⁺ T cells capable of IFN- synthesis.

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