Abstract

Enteroviruses are a major cause of human disease. Adipose-specific phospholipase A2 (PLA2G16) was recently identified as a pan-enterovirus host factor and potential drug target. In this study, we identify a possible mechanism of PLA2G16 evasion by employing a dual glycan receptor-binding enterovirus D68 (EV-D68) strain. We previously showed that this strain does not strictly require the canonical EV-D68 receptor sialic acid. Here, we employ a haploid screen to identify sulfated glycosaminoglycans (sGAGs) as its second glycan receptor. Remarkably, engagement of sGAGs enables this virus to bypass PLA2G16. Using cryo-EM analysis, we reveal that, in contrast to sialic acid, sGAGs stimulate genome release from virions via structural changes that enlarge the putative openings for genome egress. Together, we describe an enterovirus that can bypass PLA2G16 and identify additional virion destabilization as a potential mechanism to circumvent PLA2G16.

Details

Title
Bypassing pan-enterovirus host factor PLA2G16
Author
Baggen, Jim 1 ; Liu, Yue 2 ; Lyoo, Heyrhyoung 1   VIAFID ORCID Logo  ; Arno L W van Vliet 1 ; Wahedi, Maryam 1 ; de Bruin, Jost W 1 ; Roberts, Richard W 1 ; Overduin, Pieter 3 ; Meijer, Adam 3 ; Rossmann, Michael G 2 ; Thibaut, Hendrik Jan 1   VIAFID ORCID Logo  ; Frank J M van Kuppeveld 1 

1  Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands 
2  Department of Biological Sciences, Purdue University, West Lafayette, IN, USA 
3  Virology Division, Centre for Infectious Diseases Research, Diagnostics and Screening, National Institute for Public Health and the Environment, Bilthoven, The Netherlands 
Pages
1-10
Publication year
2019
Publication date
Jul 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-11256-z
ProQuest document ID
2260061763
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.