Mutations on the FG surface loop of human papillomavirus type 16 major capsid protein affect recognition by both type-specific neutralizing antibodies and cross-reactive antibodies

• Published in: Journal of medical virology Vol. 77; no. 4; pp. 558 - 565
• Main Authors: Carpentier, Guillaume S., Fleury, Maxime J.J., Touzé, Antoine, Sadeyen, Jean-Rémy, Tourne, Sylvie, Sizaret, Pierre-Yves, Coursaget, Pierre
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2005; Wiley-Liss; Wiley-Blackwell
• Subjects: Antibodies, Monoclonal - immunology; Antibodies, Viral - biosynthesis; Antibodies, Viral - immunology; Biological and medical sciences; Capsid Proteins - chemistry; Capsid Proteins - genetics; Capsid Proteins - immunology; chimeric VLPs; Cross Reactions; Epitopes - chemistry; Fundamental and applied biological sciences. Psychology; HPV; Human papillomavirus; Human papillomavirus 16; Human viral diseases; Humans; Infectious diseases; Life Sciences; Medical sciences; Microbiology; Miscellaneous; monoclonal antibodies; Mutation; Neutralization Tests; neutralizing epitopes; Oncogene Proteins, Viral - chemistry; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - immunology; Papillomaviridae - genetics; Papillomaviridae - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Viral diseases; Virion - immunology; Virology; Antigenic determinant; Papovaviridae; Monoclonal antibody; Neutralizing antibody; Protein; HPV; Papillomavirus; Virus; Human papillomavirus 16; chimeric VLPs; Human papillomavirus; Mutation; neutralizing epitopes; Capsid; Recognition; monoclonal antibodies
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.20492

The aim of this study was to further characterize the conformational neutralizing epitopes present on the surface‐exposed FG loop of human papillomavirus (HPV) type 16 L1 major capsid protein. We have generated previously two chimeric L1 proteins by insertion of a foreign peptide encoding an epitope of the hepatitis B core (HBc) antigen within the FG loop. In addition, three other chimeric L1 proteins were obtained by replacing three different FG loop sequences by the HBc motif and three others by point mutations. All these chimeric L1 proteins retained the ability to self‐assemble into virus‐like particles (VLPs), with the exception of the mutant with substitution of the L1 sequence 274–279 by the HBc motif. The eight chimeric VLPs were then analyzed for differential reactivity with a set of six HPV‐16 and HPV‐31 monoclonal antibodies that bound to conformational and linear epitopes. The binding patterns of these monoclonal antibodies confirmed that the FG loop contained or contributed to neutralizing conformational epitopes. The results obtained suggested that the H31.F7 antibody, an anti‐HPV‐31 cross‐reacting and neutralizing antibody, recognized a conformational epitope situated before the 266–271 sequence. In addition, H16.E70 neutralizing antibody reactivity was reduced with L1 VLPs with an Asn to Ala point mutation at position 270, suggesting that Asn is a part of the epitope recognized by this antibody. This study contributes to the understanding of the antigenic structure of HPV‐16 and ‐31 L1 proteins by confirming that the FG loop contributes to neutralizing epitopes and suggesting the existence of both type‐specific and cross‐reactive conformational epitopes within the FG loop. J. Med. Virol. 77:558–565, 2005. © 2005 Wiley‐Liss, inc.