The fusion glycoprotein of human respiratory syncytial virus facilitates virus attachment and infectivity via an interaction with cellular heparan sulfate

Human respiratory syncytial virus (RSV) F glycoprotein (RSV-F) can independ ently interact with immobilized heparin and facilitate both attachment to a nd infection of cells via an interaction with cellular heparan sulfate. RSV -glycosaminoglycan (GAG) interactions were evaluated using heparin agarose affinity chromatography. RSV-F from A2- and B1/cp-52 (cp-52)-infected cell lysates, RSV F derived from a recombinant vaccinia virus, and affinity-puri fied F protein all bound to and were specifically eluted from heparin colum ns. In infectivity inhibition studies, soluble GAGs decreased the infectivi ty of RSV A2 and cp-52, with bovine lung heparin exhibiting the highest spe cific activity against both A2 (50% effective dose [ED50] = 0.28 +/- 0.11 m u g/ml) and cp-52 (ED50 = 0.55 +/- 0.14 mu g/ml). Furthermore, enzymatic di gestion of cell surface GAGs by heparin lyase I and heparin lyase III but n ot chondroitinase ABC resulted in a significant reduction in cp-52 infectiv ity. Moreover, bovine lung heparin inhibited radiolabeled A2 and cp-52 viru s binding up to 30%. Taken together, these data suggest that RSV-F independ ently interacts with heparin/heparan sulfate and this type of interaction f acilitates virus attachment and infectivity.