University of Groningen
Membrane fusion of influenza and chikungunya viruses
Blijleven, Jelle
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Publication date: 2018
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Blijleven, J. (2018). Membrane fusion of influenza and chikungunya viruses: Mechanisms inferred from single-particle experiments. Rijksuniversiteit Groningen.
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Membrane fusion of influenza and chikungunya viruses Mechanisms inferred from single-particle experiments
Jelle Blijleven 2018
Cover design: Jelle Blijleven Printing house: GVO
Zernike Institute PhD thesis series: 2018-26
ISSN: 1570-1530
ISBN (print): 978-94-034-0838-5 ISBN (digital): 978-94-034-0837-8
The research described in this thesis was carried out at and supported by the Zernike Institute for Advanced Materials of the University of Groningen, the Netherlands.
Copyright © 2018 by Jelle S. Blijleven. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means without the prior written permission of the author.
Membrane fusion of influenza and
chikungunya viruses
Mechanisms inferred from single-particle experiments
Proefschrift
ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen
op gezag van de
rector magnificus prof. dr. E. Sterken en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op vrijdag 21 september 2018 om 14.30 uur
door
Jelle Simon Blijleven
geboren op 22 november 1987Promotores
Prof. dr. A.M. van Oijen Prof. dr. ir. E. van der Giessen Beoordelingscommissie Prof. dr. S. Daniel
Prof. dr. A.L.W. Huckriede Prof. dr. J.A. Killian
v
Contents
1 Introduction ... 7
1.1 Enveloped viruses and disease 8
1.2 Influenza virus 8
1.3 Chikungunya virus 10
1.4 Cellular entry by enveloped viruses 10 1.5 Motivation for in vitro single-particle assay 15
1.6 Thesis outline 15
2 Mechanisms of influenza viral membrane fusion ... 17
2.1 Introduction 18
2.2 Membrane fusion 19
2.3 Hemagglutinin structure and conformational rearrangement 23 2.4 Collaboration between hemagglutinins as unraveled by single-particle experiments
30
2.5 Future directions 39
2.6 Appendix 41
3 The importance of the stability of the influenza hemagglutinin globular bottom probed in
single-particle membrane fusion assays ... 43
3.1 Introduction 44 3.2 Results 48 3.3 Discussion 55 3.4 Acknowledgements 57 3.5 Methods 57 3.6 Appendix 59
4 Chikungunya virus fusion properties elucidated by single-particle and bulk approaches 65
4.1 Introduction 66 4.2 Results 67 4.3 Discussion 73 4.4 Methods 76 4.5 Acknowledgements 78 4.6 Appendix 79
vi
5 Cooperative activity between fusion proteins mediates chikungunya virus fusion and is
inhibited by sub-stoichiometric antibody binding ... 83
5.1 Introduction 84 5.2 Results 85 5.3 Discussion 95 5.4 Methods 97 5.5 Appendix 100 6 Scientific summary and perspectives ... 109
6.1 Summary 110 6.2 Perspectives 112 References ... 114
Wetenschappelijke samenvatting ... 125
Summary for non-experts ... 128
Samenvatting voor niet-deskundigen ... 129
Acknowledgements ... 130
List of publications ... 132
