Article
Received: 6 February 2009; Revised: 21 April 2009; Accepted: 22 April 2009
10.1002/pro.156 About DOI
Identification of neutralizing conformational epitopes on the human papillomavirus type 31 major capsid protein and functional implications |
| Maxime J. J. Fleury 1 2, Antoine Touzé 1 2, Marie-Christine Maurel 3, Thierry Moreau 1, Pierre Coursaget 1 2 * |
| 1INSERM U618, Université François Rabelais, Tours, France 2IFR136, Agents transmissibles et Infectiologie, Tours, France 3UMR 6175 INRA-CNRS-Université-Haras, Nationaux, Reproduction Physiology and Behalf, Nouzilly, France |
| email: Pierre Coursaget (coursaget@univ-tours.fr) |
*Correspondence to Pierre Coursaget, INSERM U618, Université François Rabelais, Tours, France
Funded by:
Ligue Contre le Cancer (Comités départementaux d'Indre et Loire et de l'Indre), Vaincre la Mucoviscidose Ministère de l'Enseignement Supérieur et de la Recherche
| Keywords |
| HPV31 L1 protein conformational epitope bacterial surface display neutralization |
| Abstract |
| The aim of this study was to characterize the conformational neutralizing epitopes of the major capsid protein of human papillomavirus type 31. Analysis of the epitopes was performed by competitive epitope mapping using 15 anti-HPV31 and by reactivity analysis using a HPV31 mutant with an insertion of a seven-amino acid motif within the FG loop of the capsid protein. Fine mapping of neutralizing conformational epitopes on HPV L1 was analyzed by a new approach using a system displaying a combinatorial library of constrained peptides exposed on E. coli flagella. The findings demonstrate that the HPV31 FG loop is dense in neutralizing epitopes and suggest that HPV31 MAbs bind to overlapping but distinct epitopes on the central part of the FG loop, in agreement with the exposure of the FG loop on the surface of HPV VLPs, and thus confirming that neutralizing antibodies are mainly located on the tip of capsomeres. In addition, we identified a crossreacting and partially crossneutralizing conformational epitope on the relatively well conserved N-terminal part of the FG loop. Moreover, our findings support the hypothesis that there is no correlation between neutralization and the ability of MAbs to inhibit VLP binding to heparan sulfate, and confirm that the blocking of virus attachment to the extracellular matrix is an important mechanism of neutralization. |
Received: 6 February 2009; Revised: 21 April 2009; Accepted: 22 April 2009
| Digital Object Identifier (DOI) |
10.1002/pro.156 About DOI
