CELL-MEMBRANE BOUND N-ACETYLNEURAMINIC ACID IS INVOLVED IN THE INFECTION OF FIBROBLASTS AND PHORBOL-ESTER DIFFERENTIATED MONOCYTE-LIKE CELLS WITH HUMAN CYTOMEGALOVIRUS (HCMV)

We focused on the role of membrane bound sugar residues in the infecti on of fibroblasts and monocyte-like cells with human cytomegalovirus ( HCMV). Treatment of phorbol 12-myristate 13-acetate (PMA) differentiat ed monocyte-like cells THP-1 or human fibroblasts MRC-5 with lectins s pecific for N-acetylneuraminic acid (NeuAc) blocked infection with HCM V. HCMV failed to infect sialidase-treated differentiated THP-1 cells or MRC-5 cells. By using NeuAc, N-glycolylneuraminic acid (NeuGl) and alpha 2-3, but not alpha 2-6, sialyloligosaccharide, the infection of cells was less efficient. NeuAc was more potent inhibitor than NeuGl. These observations suggest that the sialic acid specificity and the na ture of the interglycosidic linkage at the end of the complex carbohyd rates may play an important role. Analogous experiments indicated that HCMV binds to N-acetylglucosamine (GlcNAc) in addition to NeuAc. Huma n cytomegalovirus infection in differentiated THP-1 cells and in human fibroblasts was inhibited by incubation of the virus with 20 mu g/ml of heparin before and during the adsorption period. Treatment of the c ells with heparinase or heparitinase inhibited infection with HCMV. We emphasized the role of NeuAc and GlcNAc and heparan sulfate proteogly cans at the surface of the cells, in the early steps of infection of b oth human fibroblasts and PMA differentiated monocyte-like cells with HCMV.