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Differential effects of HSV-1 and HCMV infection on adhesion molecule expression on human corneal keratocytes
P M Stuart1, N Usui, R S Randhawa
1Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
Purpose:
Previous studies have shown that keratoplasty buttons obtained at surgery from patients with herpes simplex virus-1 (HSV-1) keratitis have elevated localized expression of the adhesion molecule ICAM-1, which plays a critical role in the initiation and amplification of an immune response. We performed studies to determine whether changes in expression of ICAM-1 and HLA class I are direct effects of productive infection of human corneal fibroblasts with HSV-1.
Methods:
Immunocytologic and flow cytometric analyses were performed to analyze the ability of HSV-1 to induce ICAM-1 and HLA class I expression in a primary cornea-derived keratocyte cell line, E-2. Positive controls for these experiments were E-2 cells infected with human cytomegalovirus (HCMV), which has been shown to increase ICAM-1 expression in selected cells, and E-2 cells treated with IFN-gamma, which upregulates both ICAM-1 and HLA class I expression in most cell types.
Results:
Kinetic cytometric analysis indicated decreased ICAM-1 expression 3 hours following HSV-1 infection of E-2 cells. In contrast, HCMV led to detectable increases in ICAM-1 expression starting 6 hours after infection. Infections with either HSV-1 or HCMV resulted in reduced HLA class I expression on E-2 and SF cells.
Conclusions:
These studies suggest that increased ICAM-1 expression seen on corneal stromal cells during clinical HSV-1 infection is not a direct result of productive viral infection, but of other mechanisms such as cytokine release by infiltrating mononuclear cells.