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Viruses 2017, 9(7), 169; doi:10.3390/v9070169

2BC Non-Structural Protein of Enterovirus A71 Interacts with SNARE Proteins to Trigger Autolysosome Formation

1
Department of Medical Microbiology, Faculty of Medicine, University Malaya, 50603 Kuala Lumpur, Malaysia
2
CIRI, International Center for Infectiology Research, Université de Lyon, 69007 Lyon, France
3
INSERM, U1111, 69007 Lyon, France
4
CNRS, UMR5308, 69007 Lyon, France
5
Ecole Normale Supérieure de Lyon, 69007 Lyon, France
6
Université Lyon 1, Centre International de Recherche en Infectiologie, 69365 Lyon, France
7
Department of Biosciences, Division of Biochemistry and Biotechnology, University of Helsinki, 00014 Helsinki, Finland
8
Institut Universitaire de France, 75231 Paris, France
9
Equipe labellisée Fondation pour la Recherche Médicale FRM, 75007 Paris, France
*
Author to whom correspondence should be addressed.
Academic Editor: Christian Münz
Received: 17 March 2017 / Revised: 19 June 2017 / Accepted: 28 June 2017 / Published: 4 July 2017
(This article belongs to the Special Issue Viruses and Autophagy)
View Full-Text   |   Download PDF [3803 KB, uploaded 4 July 2017]   |  

Abstract

Viruses have evolved unique strategies to evade or subvert autophagy machinery. Enterovirus A71 (EV-A71) induces autophagy during infection in vitro and in vivo. In this study, we report that EV-A71 triggers autolysosome formation during infection in human rhabdomyosarcoma (RD) cells to facilitate its replication. Blocking autophagosome-lysosome fusion with chloroquine inhibited virus RNA replication, resulting in lower viral titres, viral RNA copies and viral proteins. Overexpression of the non-structural protein 2BC of EV-A71 induced autolysosome formation. Yeast 2-hybrid and co-affinity purification assays showed that 2BC physically and specifically interacted with a N-ethylmaleimide-sensitive factor attachment receptor (SNARE) protein, syntaxin-17 (STX17). Co-immunoprecipitation assay further showed that 2BC binds to SNARE proteins, STX17 and synaptosome associated protein 29 (SNAP29). Transient knockdown of STX17, SNAP29, and microtubule-associated protein 1 light chain 3B (LC3B), crucial proteins in the fusion between autophagosomes and lysosomes) as well as the lysosomal-associated membrane protein 1 (LAMP1) impaired production of infectious EV-A71 in RD cells. Collectively, these results demonstrate that the generation of autolysosomes triggered by the 2BC non-structural protein is important for EV-A71 replication, revealing a potential molecular pathway targeted by the virus to exploit autophagy. This study opens the possibility for the development of novel antivirals that specifically target 2BC to inhibit formation of autolysosomes during EV-A71 infection. View Full-Text
Keywords: picornavirus; enterovirus; enterovirus A71; replication; autophagy; autolysosome; syntaxin-17; synaptosome-associated protein of 29 kDa; SNARE; 2BC picornavirus; enterovirus; enterovirus A71; replication; autophagy; autolysosome; syntaxin-17; synaptosome-associated protein of 29 kDa; SNARE; 2BC
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lai, J.K.F.; Sam, I.-C.; Verlhac, P.; Baguet, J.; Eskelinen, E.-L.; Faure, M.; Chan, Y.F. 2BC Non-Structural Protein of Enterovirus A71 Interacts with SNARE Proteins to Trigger Autolysosome Formation. Viruses 2017, 9, 169.

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