Purchase this article with an account.
Balaraj Balaram Menon, Xiaohong Zhou, Sandra Spurr-Michaud, Jaya Rajaiya, James Chodosh, Ilene K Gipson; Adenovirus-induced MUC16 Ectodomain Release Correlates with Decreased Barrier Function and Increased Adenoviral Infection of Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):345.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Mechanisms used by epidemic keratoconjunctivitis (EKC)-causing adenoviruses to overcome the mucosal barrier of the ocular surface epithelium and initiate infection remain unknown. At the 2015 ARVO General Meeting, we reported that an EKC-causing adenovirus, but not a non-EKC-causing one, induces release of the ectodomain of MUC16 – a membrane-associated mucin (MAM) with barrier functions – from human corneal epithelial cells. The purpose of this study is to determine if MUC16 ectodomain release facilitates adenoviral infection of ocular surface epithelial cells.
Telomerase-immortalized human corneal-limbal epithelial (HCLE) cells, grown to confluence and allowed to differentiate for optimal mucin expression, were exposed to human adenoviruses HAdV-D37 (EKC-causing) and HAdV-D19p (non-EKC-causing) at an MOI of 3. As a measure of epithelial barrier function, rose bengal dye penetrance assays were performed on HCLE cells exposed to HAdV-D37 and HAdV-D19p for 2 h. To compare infection by HAdV-D37 and HAdV-D19p, HCLE cells were incubated independently with both adenoviruses for 2 days, following which adenoviral entry was quantified by quantitative PCR amplification of a highly conserved region of the E1B gene.
1) Rose bengal dye penetrance assays revealed a significant increase in dye uptake by HAdV-D37-exposed HCLE cells in comparison to HAdV-D19p-exposed and control cells. 2) Quantitative PCR results indicated a near 4-fold increase in E1B gene copies in HAdV-D37-incubated HCLE cells in comparison to the HAdV-D19p-incubated condition.
Collectively, these results suggest that EKC-causing adenoviruses induce MUC16 ectodomain release to disrupt epithelial barrier function and initiate infection of ocular surface epithelial cells.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
This PDF is available to Subscribers Only