Bypassing pan-enterovirus host factor PLA2G16.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31320648.
- Also identified by DOI 10.1038/s41467-019-11256-z and PMC identifier 6639302.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Enterovirus D, Human
- Glycosaminoglycans
- Phospholipases A2, Calcium-Independent
- Receptors, Virus
- Tumor Suppressor Proteins
- Virus Internalization
- Virus Uncoating