ROLE OF THE EXTRACELLULAR DOMAIN OF HUMAN HERPESVIRUS-7 GLYCOPROTEIN-B IN VIRUS BINDING TO CELL-SURFACE HEPARAN-SULFATE PROTEOGLYCANS

In an attempt to identify the human herpesvirus 7 (HHV-7) envelope pro tein(s) involved in cell surface binding, the extracellular domain of the HHV-7 glycoprotein B (gB) homolog protein was cloned and expressed as a fusion product with the Fc domain of human immunoglobulin G heav y chain gamma 1 (gB-Fc) in an eukaryotic cell system. Indirect immunof luorescence followed by pow cytometric analysis revealed specific bind ing of gB-Fc to the membrane of SupT1 cells hut not to other CD4(+) T- lymphoblastoid cell lines, such as Jurkat or PM1, clearly indicating t hat gB-Fc did not bind to the CD4 molecule. This was also suggested by the ability of gB-Fc to bind to CD4-negative fibroblastoid Chinese ha mster ovary (CHO) cells. The binding was abrogated by enzymatic remova l of cell surface heparan sulfate proteoglycans by heparinase and hepa ritinase but not by treatment with condroitinase ABC. In addition, bin ding of the gB-Fc fusion protein to CHO cells was severely impaired in the presence of soluble heparin, as well as when heparan sulfate-defi cient mutant CHO cells were used. Consistent with these findings, solu ble heparin was found to block HHV-7 infection and syncytium formation in the SupT1 cell line. Although the CD4 antigen is a critical compon ent of the receptor for the T-lymphotropic HHV-7, these findings sugge st that heparin-like molecules also play an important role in HHV-7-ce ll surface interactions required for infection and that gB represents one of the HHV-7 envelope proteins involved in the adsorption of virus -to-cell surface proteoglycans.