title: Identification of the neutralizing epitopes of Merkel cell polyomavirus major capsid protein within the BC and EF surface loops.
abstract: Merkel cell polyomavirus (MCPyV) is the first polyomavirus clearly associated with a human cancer, i.e. the Merkel cell carcinoma (MCC). Polyomaviruses are small naked DNA viruses that induce a robust polyclonal antibody response against the major capsid protein (VP1). However, the polyomavirus VP1 capsid protein epitopes have not been identified to date. The aim of this study was to identify the neutralizing epitopes of the MCPyV capsid. For this goal, four VP1 mutants were generated by insertional mutagenesis in the BC, DE, EF and HI loops between amino acids 88-89, 150-151, 189-190, and 296-297, respectively. The reactivity of these mutants and wild-type VLPs was then investigated with anti-VP1 monoclonal antibodies and anti-MCPyV positive human sera. The findings together suggest that immunodominant conformational neutralizing epitopes are present at the surface of the MCPyV VLPs and are clustered within BC and EF loops.
authors: L'UNAM Université, Groupe d'Etude des Interactions Hôte-Pathogène, UPRES EA 3142, Université d'Angers, Angers, France.
authors: Maxime J J
authors: MJ
authors: Fleury
authors: UMR INRA 1282, Virologie et Immunologie Moléculaire, Faculté des Sciences Pharmaceutiques, Université François Rabelais, PRES Centre-Val de Loire Université, Tours, France.
authors: Jérôme T J
authors: JT
authors: Nicol
authors: UMR INRA 1282, Virologie et Immunologie Moléculaire, Faculté des Sciences Pharmaceutiques, Université François Rabelais, PRES Centre-Val de Loire Université, Tours, France; CHRU de Tours-Hôpital Trousseau, Service de Dermatologie, Tours, France.
authors: Mahtab
authors: M
authors: Samimi
authors: UMR INRA 1282, Virologie et Immunologie Moléculaire, Faculté des Sciences Pharmaceutiques, Université François Rabelais, PRES Centre-Val de Loire Université, Tours, France.
authors: Françoise
authors: F
authors: Arnold
authors: UMR INRA 1282, Virologie et Immunologie Moléculaire, Faculté des Sciences Pharmaceutiques, Université François Rabelais, PRES Centre-Val de Loire Université, Tours, France.
authors: Raphael
authors: R
authors: Cazal
authors: UMR INRA 1282, Virologie et Immunologie Moléculaire, Faculté des Sciences Pharmaceutiques, Université François Rabelais, PRES Centre-Val de Loire Université, Tours, France.
authors: Raphaelle
authors: R
authors: Ballaire
authors: UMR INRA 1282, Virologie et Immunologie Moléculaire, Faculté des Sciences Pharmaceutiques, Université François Rabelais, PRES Centre-Val de Loire Université, Tours, France.
authors: Olivier
authors: O
authors: Mercey
authors: UMR INRA 1282, Virologie et Immunologie Moléculaire, Faculté des Sciences Pharmaceutiques, Université François Rabelais, PRES Centre-Val de Loire Université, Tours, France.
authors: Hélène
authors: H
authors: Gonneville
authors: UMR INRA 1282, Virologie et Immunologie Moléculaire, Faculté des Sciences Pharmaceutiques, Université François Rabelais, PRES Centre-Val de Loire Université, Tours, France.
authors: Nicolas
authors: N
authors: Combelas
authors: UMR INRA 1282, Biologie des virus aviaires, INRA Nouzilly, France.
authors: Jean-Francois
authors: JF
authors: Vautherot
authors: UMR INSERM 1100, Mécanismes Protéolytiques dans l'Inflammation, Faculté de Médecine, Université François Rabelais, PRES Centre-Val de Loire Université, Tours, France.
authors: Thierry
authors: T
authors: Moreau
authors: UMR INRA 1282, Virologie et Immunologie Moléculaire, Faculté des Sciences Pharmaceutiques, Université François Rabelais, PRES Centre-Val de Loire Université, Tours, France; CHRU de Tours-Hôpital Trousseau, Service de Dermatologie, Tours, France.
authors: Gérard
authors: G
authors: Lorette
authors: Faculté des Sciences Pharmaceutiques, Université François Rabelais, PRES Centre-Val de Loire Université, Tours, France.
authors: Pierre
authors: P
authors: Coursaget
authors: UMR INRA 1282, Virologie et Immunologie Moléculaire, Faculté des Sciences Pharmaceutiques, Université François Rabelais, PRES Centre-Val de Loire Université, Tours, France.
authors: Antoine
authors: A
authors: Touzé
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D003429:Cross Reactions / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D059965:Merkel cell polyomavirus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D016056:Immunodominant Epitopes