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A. V. Chintakuntlawar, R. A. Astley, J. Chodosh; Viral Capsid Mediates Expression of Chemokine KC/CXCL1 in Adenovirus Keratitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2825. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Epidemic keratoconjunctivitis (EKC) is a highly contagious adenoviral ocular syndrome characterized by a delayed onset influx of leukocytes into the corneal stroma. Pathogenesis of the chronic keratitis in EKC appears to depend upon chemokine expression and subsequent neutrophil infiltration. The chemokine KC/CXCL1 is a paradigm chemoattractant for neutrophils. In this study, we sought to determine the role of KC in neutrophil influx and the contribution of specific viral components towards KC expression in the mouse model of adenovirus keratitis.
8-12 week old wild type (WT) or KC knock out (KC -/-) C57Bl/6J mice were used for these experiments. Virus-free buffer, human adenovirus type 37 (HAdV-37, 102 or 105 TCID), UV-inactivated HAdV-37, heat-inactivated HAdV-37, empty HAdV-37 capsid, or HAdV-37 genomic DNA were injected into the corneal stroma by a gas powered micro-injection system. The degree of keratitis was determined by clinical examination and histopathology. Chemokine expression was quantified by ELISA. Infiltrating leukocytes were characterized by flow cytometry.
At 1 and 4 days post-infection, KC -/- mice showed clinical disease similar to WT mice but less neutrophil infiltration by both histopathology and flow cytometry. UV-inactivated but not heat-inactivated virus induced keratitis and chemokine expression comparable to intact HAdV-37. The quantity of KC expression 16 hours after empty capsid injection fell between that induced by 102 TCID and 105 TCID intact HAdV-37. Transfection of HAdV-37 DNA did not induce KC expression.
The upregulation of KC by HAdV-37 infection was important for the infiltration of neutrophils into the cornea, but neither viral replication or viral gene expression was essential for the development of corneal inflammation in the mouse model of adenovirus keratitis. Empty adenoviral capsid, but not viral DNA, induced expression of KC in the murine cornea, suggesting that binding of HAdV-37 capsid to a cellular receptor within the corneal stroma mediates subsequent adenovirus keratitis in this model.
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