THE CELL-SURFACE RECEPTOR IS A MAJOR DETERMINANT RESTRICTING THE HOST-RANGE OF THE B-LYMPHOTROPIC PAPOVAVIRUS

The B-lymphotropic papovavirus (LPV) productively infects only a subse t of human B-lymphoma-derived cell lines while transfection of the vir al genome yields infectious viral particles in a much wider variety of human hematopoietic cell lines. We have analyzed the contribution of a putative LPV receptor on the cell surface of B-cell lines in restric ting the virus host range. In order to establish a quantitative virus binding assay for LPV, infectious virus particles were highly purified by metrizamide equilibrium density centrifugation and used as immunog ens to raise seven mouse monoclonal antibodies specific for LPV VP1. V irus particle binding was quantitated in an indirect, nonradioactive a ssay with an LPV VP1-specific enzyme-linked immunosorbent assay. Bindi ng of LPV particles to permissive human B-lymphoma cell line BJA-B occ ured within minutes. Kinetics and capacity of binding were similar at 4 and 37-degrees-C. A BJA-B cell was estimated to bind approximately 6 00 virus particles at conditions under which 50% of the administered v irus was bound. The sialidase and trypsin sensitivities of the cellula r virus binding moiety show that sialylated and proteinaceous componen ts are necessary components of the LPV receptor on BJA-B cells. Despit e a high binding capacity of BJA-B cells for simian virus 40, LPV bind ing was not significantly affected by a 20-fold excess of simian virus 40 particles, indicating that these related polyomaviruses do not bin d to the same receptor on BJA-B cells. Reduction of LPV binding to sia lidase-pretreated BJA-B cells was accompanied by a similar reduction o f infection, indicating that virus binding may be a limiting factor in the LPV replicative cycle. The two highly LPV-permissive human B-lymp homa cell lines BJA-B and Namalwa displayed high virus binding whereas low and nonpermissive hematopoietic cell lines showed reduced or unde tectable virus binding. We conclude that the inability of LPV particle s to productively infect the nonpermissive human hematopoietic cell li nes analyzed is probably due to the absence or insufficient expression of a functional cell surface receptor.