Bypassing pan-enterovirus host factor PLA2G16

Jim Baggen, Yue Liu, Heyrhyoung Lyoo, Arno L. W. Vliet, Maryam Wahedi, Jost W. Bruin, Richard W. Roberts, Pieter Overduin, Adam Meijer, Michael G. Rossmann, Hendrik Jan Thibaut and Frank J. M. Kuppeveld ()
Additional contact information
Jim Baggen: Utrecht University
Yue Liu: Purdue University
Heyrhyoung Lyoo: Utrecht University
Arno L. W. Vliet: Utrecht University
Maryam Wahedi: Utrecht University
Jost W. Bruin: Utrecht University
Richard W. Roberts: Utrecht University
Pieter Overduin: Diagnostics and Screening, National Institute for Public Health and the Environment
Adam Meijer: Diagnostics and Screening, National Institute for Public Health and the Environment
Michael G. Rossmann: Purdue University
Hendrik Jan Thibaut: Utrecht University
Frank J. M. Kuppeveld: Utrecht University

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11256-z

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