Bypassing pan-enterovirus host factor PLA2G16.
Nat Commun
; 10(1): 3171, 2019 07 18.
Article
en En
| MEDLINE
| ID: mdl-31320648
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Receptores Virales
/
Enterovirus Humano D
/
Proteínas Supresoras de Tumor
/
Internalización del Virus
/
Fosfolipasas A2 Calcio-Independiente
/
Desencapsidación Viral
/
Glicosaminoglicanos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2019
Tipo del documento:
Article