Bypassing pan-enterovirus host factor PLA2G16

Jim Baggen; Yue Liu; Heyrhyoung Lyoo; Arno L W van Vliet; Maryam Wahedi; Jost W de Bruin; Richard W Roberts; Pieter Overduin; Adam Meijer; Michael G Rossmann; Hendrik Jan Thibaut; Frank J M van Kuppeveld

doi:10.1038/s41467-019-11256-z

Bypassing pan-enterovirus host factor PLA2G16

Jim Baggen
, Yue Liu
, Heyrhyoung Lyoo
, Arno L W van Vliet
, Maryam Wahedi
, Jost W de Bruin
, Richard W Roberts
, Pieter Overduin
, Adam Meijer
, Michael G Rossmann
, Hendrik Jan Thibaut
, Frank J M van Kuppeveld

Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA.
Utrecht University
Virology Division, Centre for Infectious Diseases Research, Diagnostics and Screening, National Institute for Public Health and the Environment, 3720 BA, Bilthoven, The Netherlands.

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	3171
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11256-z
Publication status	Published - 18 Jul 2019

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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title = "Bypassing pan-enterovirus host factor PLA2G16",

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.",

author = "Jim Baggen and Yue Liu and Heyrhyoung Lyoo and \{van Vliet\}, \{Arno L W\} and Maryam Wahedi and \{de Bruin\}, \{Jost W\} and Roberts, \{Richard W\} and Pieter Overduin and Adam Meijer and Rossmann, \{Michael G\} and Thibaut, \{Hendrik Jan\} and \{van Kuppeveld\}, \{Frank J M\}",

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AU - Baggen, Jim

AU - Liu, Yue

AU - Lyoo, Heyrhyoung

AU - van Vliet, Arno L W

AU - Wahedi, Maryam

AU - de Bruin, Jost W

AU - Roberts, Richard W

AU - Overduin, Pieter

AU - Meijer, Adam

AU - Rossmann, Michael G

AU - Thibaut, Hendrik Jan

AU - van Kuppeveld, Frank J M

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N2 - 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.

AB - 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.

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JO - Nature Communications

JF - Nature Communications

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M1 - 3171

ER -

Bypassing pan-enterovirus host factor PLA2G16

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