2 ANTIBODIES THAT NEUTRALIZE PAPILLOMAVIRUS BY DIFFERENT MECHANISMS SHOW DISTINCT BINDING PATTERNS AT 13 ANGSTROM RESOLUTION

Complexes between bovine papillomavirus type 1 (BPV1) and examples of two sets of neutralizing, monoclonal antibodies (mAb) to the major cap sid protein (L1) were analyzed by low-dose cryo-electron microscopy an d three-dimensional (3D) image reconstruction to 13 Angstrom resolutio n. mAb #9 is representative of a set of neutralizing antibodies that c an inhibit viral binding to the cell surface, while mAb 5B6 is represe ntative of a second set that efficiently neutralizes papillomaviruses without significantly inhibiting viral binding to the cell surface. Th e 3D reconstructions reveal that mAb #9 binds to L1 molecules of both pentavalent and hexavalent capsomeres. In contrast, 5B6 binds only to hexavalent capsomeres, reflecting the significant structural or enviro nmental differences for the 5B6 epitope in the 12 pentavalent capsomer es. Epitope localization shows that mAb #9 binds monovalently to the t ips of capsomeres whereas 5B6 binds both monovalently and bivalently t o the sides of hexavalent capsomeres approximately two-thirds of the w ay down from the outer tips, very close to the putative stabilizing in tercapsomere connections. The absence of mAb 5B6 from the pentavalent capsomeres and its inability to prevent viral binding to the cell surf ace suggest that receptor binding may occur at one or more of the 12 v irion vertices. (C) 1998 Academic Press