Identification of the neutralizing epitopes of Merkel cell polyomavirus major capsid protein within the BC and EF surface loops.

Maxime J J Fleury,Antoine Touzé,Thierry Moreau,Nicolas Combelas,Mahtab Samimi,Pierre Coursaget,Gérard Lorette,Jérôme T J Nicol,Françoise Arnold,Hélène Gonneville,Olivier Mercey,Jean-Francois Vautherot,Raphael Cazal,Raphaelle Ballaire

doi:10.1371/journal.pone.0121751

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.

Highlights

Polyomaviruses are known to infect mammals and birds
In order to identify the major Merkel cell polyomavirus (MCPyV) VP1 conformational epitopes, we investigated the reactivity of wild-type and four VP1 protein insertional mutants against a panel of anti-MCPyV VP1 monoclonal antibodies and anti-MCPyV positive human sera
The strategy adopted to map immuno-dominant epitopes of the MCPyV VP1 capsid protein is based on the assumption that the hypervariable loops at the capsomer surface contain doi:10.1371/journal.pone.0121751.g004

Summary

Introduction

Thirteen human polyomavirus have been identified to date including BKPyV [1], JCPyV [2], KIPyV [3], WUPyV [4], Merkel cell polyomavirus (MCPyV) [5], HPyV6 and HPyV7 [6], TSPyV [7], HPyV9 [8], MWPyV [9,10,11], STLPyV [12], HPyV12 [13] and NJPyV [14]. MCPyV has been associated with Merkel cell carcinoma (MCC) and is recognized as a 2A carcinogen by IARC [15]. MCC is a relatively rare but aggressive skin cancer with a mortality rate higher than melanoma. MCC is rarely observed in people younger than 50 years of age, and the risk of developing.

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Conclusion