Structural and functional analysis of natural capsid variants suggests sialic acid-independent entry of BK polyomavirus
Marie N. Sorin,
Antonio Di Maio,
Lisete M. Silva,
Domenic Ebert,
Clément P. Delannoy,
Ngoc-Khanh Nguyen,
Yann Guerardel,
Wengang Chai,
Franck Halary,
Karine Renaudin-Autain,
Yan Liu,
Céline Bressollette-Bodin,
Thilo Stehle,
Dorian McIlroy
Affiliations
Marie N. Sorin
Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, 44000 Nantes, France; Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany
Antonio Di Maio
Glycoscience Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
Lisete M. Silva
Glycoscience Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
Domenic Ebert
Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany
Clément P. Delannoy
Université de Lille, CNRS, UMR 8576 – UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France
Ngoc-Khanh Nguyen
Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, 44000 Nantes, France
Yann Guerardel
Université de Lille, CNRS, UMR 8576 – UGSF - Unité de Glycobiologie Structurale et Fonctionnelle, 59000 Lille, France; Institute for Glyco-core Research (iGCORE), Gifu University, Gifu, Japan
Wengang Chai
Glycoscience Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
Franck Halary
Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, 44000 Nantes, France
Karine Renaudin-Autain
CHU Nantes Service d'Anatomie et Cytologie Pathologique, Nantes, France
Yan Liu
Glycoscience Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
Céline Bressollette-Bodin
Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, 44000 Nantes, France; CHU Nantes Laboratoire de Virologie, Nantes, France; Faculté de Médecine, Nantes Université, Nantes, France
Thilo Stehle
Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany
Dorian McIlroy
Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, 44000 Nantes, France; Faculté des Sciences et des Techniques, Nantes Université, Nantes, France; Corresponding author
Summary: BK polyomavirus (BKPyV) is an opportunistic pathogen that uses the b-series gangliosides GD1b and GT1b as entry receptors. Here, we characterize the impact of naturally occurring VP1 mutations on ganglioside binding, VP1 protein structure, and virus tropism. Infectious entry of single mutants E73Q and E73A and the triple mutant A72V-E73Q-E82Q (VQQ) remains sialic acid dependent, and all three variants acquire binding to a-series gangliosides, including GD1a. However, the E73A and VQQ variants lose the ability to infect ganglioside-complemented cells, and this correlates with a clear shift of the BC2 loop in the crystal structures of E73A and VQQ. On the other hand, the K69N mutation in the K69N-E82Q variant leads to a steric clash that precludes sialic acid binding. Nevertheless, this mutant retains significant infectivity in 293TT cells, which is not dependent on heparan sulfate proteoglycans, implying that an unknown sialic acid-independent entry receptor for BKPyV exists.
