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D. Shukla, V. Tiwari, C. Clement, T. Valyi–Nagy, B.Y. J. T. Yue; Differences in Receptor Usages by Herpes Simplex Virus–1 for Entry into Ocular Cell Types . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3038.
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The goal of this study was to identify the receptor used by herpes simplex virus–1 (HSV–1) for entry into cultured human corneal fibroblasts (CF) and trabecular meshwork (TM) cells
To verify the natural susceptibility of CF and TM cells in vitro, the cells were exposed to ß–galactosidase–expressing and enhanced green fluorescent protein–expressing HSV–1 virions. Deconvolution and confocal microscopy were used to monitor entry into live cells. Immunohistochemistry and reverse transcriptase–PCR were used to examine entry receptor expression in the ocular cell types. Blocking of entry by receptor specific antibodies was used as a means to verify the use of receptors. In CF the expression of 3–O–sulfated heparan sulfate (3–OS HS) was also verified by disaccharide analysis of the cell surface heparan sulfate.
A three dimensional model of HSV–1 entry into CF and TM cells were generated by use of deconvolution and confocal microscopy. Expression of HSV–1 gD receptors, HVEM and 3–OS HS, but not nectin–1, was suggested by reverse transcriptase–PCR in both CF and TM. Anti–HVEM antibodies blocked HSV–1 entry into TM but not in CF. Anti–nectin–1 antibodies had no effects on HSV–1 entry into TM or CF. Entry into CF was blocked by HS hydrolyzing enzymes that specifically degraded cell surface HS. Enzymatic removal of surface HS drastically reduced gD binding to CF and HS preparations enriched in 3–OS HS specifically blocked fusion of CF with HSV–1 glycoprotein expressing CHO–K1 cells.
HSV–1 entry into ocular cell types involves different set of receptors. HVEM is primarily used for entry into TM while 3–OS HS is likely the receptor for entry into CF. In either case nectin–1 does not appear to play a significant role in entry.
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