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Journal of Virology, April 2001, p. 3077-3088, Vol. 75, No. 7
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
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
/ 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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