HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Noisakran, S. Articles by Carr, D. J. J. Search for Related Content PubMed PubMed Citation Articles by Noisakran, S. Articles by Carr, D. J. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Eye Infections

Plasmid DNA Encoding IFN-1 Antagonizes Herpes Simplex Virus Type 1 Ocular Infection Through CD4⁺ and CD8⁺ T Lymphocytes¹

Sansanee Noisakran^* and Daniel J. J. Carr^2,

^* Departments of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112; and Departments of Ophthalmology, Microbiology, and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104

The present study was undertaken to further characterize the anti-viral efficacy of a plasmid DNA encoding IFN-1 against ocular herpes simplex virus type 1 (HSV-1) infection. In mice ocularly treated with plasmid DNA encoding IFN-1, the efficacy of the transgene was inversely proportional to the amount of virus used to infect the mice. Ocular treatment of mice with the IFN-1 transgene was the only mucosal route tested that showed efficacy against ocular HSV-1 infection compared with vaginal or intranasal delivery. Mice treated with the plasmid DNA encoding IFN-1 showed a significant reduction in viral Ag expression in the eyes and trigeminal ganglion that correlated with a reduction in immune cell infiltration into the cornea and iris on days 3 and 6 postinfection, as evidenced by immunohistochemical staining. Depleting mice of either CD4⁺ or CD8⁺ T lymphocytes completely blocked the resistance to herpes simplex virus type 1-induced mortality in mice treated with the IFN-1 transgene. In the absence of infection, the application of naked DNA encoding IFN-1 significantly increased the levels of IL-6- and IFN--inducible protein 10 transcript expression in the corneas 24 h post-treatment. Expression of the plasmid construct following topical application in the eye included the rectus muscles proximal to the cornea as well as the spleen. Collectively, the protective efficacy of the IFN-1 transgene against ocular HSV-1 infection is dependent upon the local or distal participation of CD4⁺ and CD8⁺ T lymphocytes early in the course of the infection, suggesting an indirect effect of the transgene against HSV-1-induced mortality.

This article has been cited by other articles:

				N. Teleshova, J. Kenney, J. Jones, J. Marshall, G. Van Nest, J. Dufour, R. Bohm, J. D. Lifson, A. Gettie, and M. Pope CpG-C Immunostimulatory Oligodeoxyribonucleotide Activation of Plasmacytoid Dendritic Cells in Rhesus Macaques to Augment the Activation of IFN-{gamma}-Secreting Simian Immunodeficiency Virus-Specific T Cells J. Immunol., August 1, 2004; 173(3): 1647 - 1657. [Abstract] [Full Text] [PDF]

				D. J. J. Carr, J. Chodosh, J. Ash, and T. E. Lane Effect of Anti-CXCL10 Monoclonal Antibody on Herpes Simplex Virus Type 1 Keratitis and Retinal Infection J. Virol., September 15, 2003; 77(18): 10037 - 10046. [Abstract] [Full Text] [PDF]

				D. J. J. Carr and S. Noisakran The Antiviral Efficacy of the Murine Alpha-1 Interferon Transgene against Ocular Herpes Simplex Virus Type 1 Requires the Presence of CD4+, {alpha}/{beta} T-Cell Receptor-Positive T Lymphocytes with the Capacity To Produce Gamma Interferon J. Virol., August 12, 2002; 76(18): 9398 - 9406. [Abstract] [Full Text] [PDF]

				S. Lee, M. Zheng, S. Deshpande, S. K. Eo, T. A. Hamilton, and B. T. Rouse IL-12 suppresses the expression of ocular immunoinflammatory lesions by effects on angiogenesis J. Leukoc. Biol., March 1, 2002; 71(3): 469 - 476. [Abstract] [Full Text] [PDF]

				V. Soumelis, I. Scott, F. Gheyas, D. Bouhour, G. Cozon, L. Cotte, L. Huang, J. A. Levy, and Y.-J. Liu Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients Blood, August 15, 2001; 98(4): 906 - 912. [Abstract] [Full Text] [PDF]

				D. J.J. Carr, P. Härle, and B. M. Gebhardt The Immune Response to Ocular Herpes Simplex Virus Type 1 Infection Experimental Biology and Medicine, May 1, 2001; 226(5): 353 - 366. [Abstract] [Full Text]