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Pablo Argueso, Jerome Mauris, Ashley Woodward; Binding of transmembrane mucins to galectin-3 limits herpes simplex virus infection. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3217. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Galectin-3 maintains mucosal barrier function in ocular surface epithelial cells through association with transmembrane mucins on the apical glycocalyx. Here, we investigated the role of this interaction in herpes simplex virus-1 (HSV-1) infection.
Two HSV-1 strains, GHSV-UL46 and 17 syn+, were used in this study. Affinity chromatography was performed using a sepharose-conjugated galectin-3 column. siRNA targeting galectin-3 was introduced into stratified telomerase-immortalized human corneal limbal epithelial (HCLE) cells by lipofectamine-mediated transfection. Viral infection was determined by immunoblotting and plaque assays. Transmembrane mucin was isolated from HCLE cells by gel chromatography and isopycnic density gradient centrifugation. The transmembrane mucin MUC16 and nectin-1 were detected by western blotting.
By affinity chromatography, HSV-1 GHSV-UL46 and 17 syn+ bound to human galectin-3. Knockdown of galectin-3 in HCLE cells by siRNA significantly impaired viral infection without affecting levels of the virus receptor nectin-1, indicating that galectin-3 is a herpes virus entry mediator. Incubation of HCLE cells with corneal transmembrane mucin isolates, but not with albumin—a protein control lacking affinity for galectin-3—decreased viral infectivity. Competition binding assays revealed that HSV-1 failed to elute the biological counter-receptor MUC16 from galectin-3 affinity columns.
Our results suggest that HSV-1 can infect corneal epithelial cells using galectin-3, a component of the ocular surface barrier, as a cellular receptor. Transmembrane mucins in corneal epithelial cells prevent infection by limiting herpesvirus access to galectin-3 on the apical glycocalyx.
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