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Journal of Virology, April 2001, p. 3077-3088, Vol. 75, No. 7
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.7.3077-3088.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Herpes Simplex Virus-Induced Keratitis: Evaluation of the Role of Molecular Mimicry in Lesion Pathogenesis

Shilpa P. Deshpande,1 Sujin Lee,1 Mei Zheng,1 Byeongwoon Song,2 David Knipe,2 Judith A. Kapp,3 and Barry T. Rouse1,*

Department of Microbiology, University of Tennessee, Knoxville, Tennessee 379961; Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 021152; and Departments of Pathology and Ophthalmology and Winship Cancer Center, Emory University School of Medicine, Atlanta, Georgia 303223

Received 10 October 2000/Accepted 24 December 2000

Viruses are suspected but usually unproven triggering factors in autoimmunity. One favored mechanism to explain the role of viruses in the genesis of autoimmunity is molecular mimicry. An immunoinflammatory blinding lesion called herpetic stromal keratitis (HSK) that follows ocular infection with herpes simplex virus (HSV) is suggested to result from a CD4+ T-cell response to a UL6 peptide of HSV that cross-reacts with a corneal autopeptide shared with the immunoglobulin G2ab (IgG2ab) isotype. The present report reevaluates the molecular mimicry hypothesis to explain HSK pathogenesis. Our results failed to reveal cross-reactivity between the UL6 and IgG2ab peptides or between peptide reactive T cells and HSV antigens. More importantly, animals infected with HSV failed to develop responses that reacted with either peptide, and infection with a recombinant vaccinia UL6 vector failed to cause HSK, in spite of generating UL6 reactivity. Other lines of evidence also failed to support the molecular mimicry hypothesis, such as the failure to affect HSK severity upon tolerization of susceptible BALB/c and B-cell-deficient mice with IgG2ab or UL6 peptides. An additional study system revealed that HSK could be induced in mouse strains, such as the OT2 × RAG1-/- mice (T cell receptor transgenic recognizing OVA323-339) that were unable to produce CD4+ T-cell responses to any detectable HSV antigens. Our results cast doubt on the molecular mimicry hypothesis as an explanation for the pathogenesis of HSK and indicate that if autoimmunity is involved its likely proceeds via a bystander activation mechanism.

* Corresponding author. Mailing address: Department of Microbiology, M409 Walters Life Sciences Bldg., University of Tennessee, Knoxville, TN 37996-0845. Phone: (865) 974-4026. Fax: (865) 974-4007. E-mail: btr{at}utk.edu.

Journal of Virology, April 2001, p. 3077-3088, Vol. 75, No. 7
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.7.3077-3088.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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Copyright © 2001 by the American Society for Microbiology. All rights reserved.