title: Mutations in human papillomavirus type 16 L1 hypervariable surface-exposed loops affect L2 binding and DNA encapsidation.
abstract: Prophylactic vaccines against human papillomavirus (HPV) based on virus-like particles (VLP) induce type-specific neutralizing antibodies against a small number of hypervariable residues positioned in surface-exposed loops of the major capsid protein L1. To investigate the importance of these residues for neutralization, cross-neutralization, L2 incorporation and genome encapsidation, ten surface-exposed amino acid residues in four hypervariable loops of L1 were mutated. VLPs containing mutated or WT L1, with or without WT L2, were produced in 293TT cells using pseudovirion expression vectors. The mutations reduced the ability to induce neutralizing antibodies and to incorporate the L2 protein in the capsid. Ability to induce cross-neutralizing antibodies and to encapsidate pseudogenomes were completely abrogated. In summary, the surface-exposed L1 loops are important for the function of the HPV particle.
authors: Department of Laboratory Medicine, Medical Microbiology, Skåne University Hospital, Lund University, Jan Waldenströms gata 59, 20502, Malmö, Sweden.
authors: Helena
authors: H
authors: Faust
authors: Departments of Laboratory Medicine, Medical Epidemiology and Biostatistics, Karolinska Institute and Karolinska Hospital, Nobels väg 12, 171 77, Stockholm, Sweden.|Department of Laboratory Medicine, Medical Microbiology, Skåne University Hospital, Lund University, Jan Waldenströms gata 59, 20502, Malmö, Sweden.
authors: Joakim
authors: J
authors: Dillner
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000378:metabolism*; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D019065:Virus Assembly
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D036022:Capsid Proteins; D004279:DNA, Viral; C063316:L2 protein, Human papillomavirus type 16; D050505:Mutant Proteins; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16