Summary auto-generated
This study identifies integrin αvβ3 (vitronectin receptor) as a candidate receptor for the virulent echovirus 9 strain Barty (E9/Barty), which causes paralysis in newborn mice. In contrast, the apathogenic prototype strain Hill uses a different receptor. The key distinction between these strains is an RGD motif insertion in the C-terminal region of the VP1 structural protein found only in E9/Barty. Using competition binding assays and antibody inhibition experiments in cell culture, researchers demonstrated that E9/Barty shares receptor specificity with coxsackievirus A9, both binding through the RGD motif to αvβ3 integrin. Antibodies against the vitronectin receptor significantly inhibited E9/Barty attachment and plaque formation, but had no effect on E9/Hill. Additionally, viral replication in mouse muscle tissue decreased dramatically with age, with no virus replication detected in mice older than one week. Since αvβ3 integrin expression is down-regulated during muscle cell development, the authors conclude that susceptibility to E9/Barty infection depends on the developmental stage and availability of this integrin receptor in murine muscle tissue.
Key findings
- E9/Barty binds to cells via an RGD motif in VP1 that interacts with integrin αvβ3 (vitronectin receptor), whereas the apathogenic E9/Hill strain uses a different receptor
- E9/Barty shares receptor specificity with coxsackievirus A9, both utilizing αvβ3 integrin for cell attachment
- Antibodies against vitronectin receptor inhibit E9/Barty attachment and plaque formation but not E9/Hill, confirming RGD-mediated receptor binding
- Viral replication in mouse muscle tissue decreases dramatically with age, with no detectable replication in mice older than one week
- Age-dependent susceptibility to E9/Barty infection correlates with developmental down-regulation of αvβ3 integrin expression in muscle tissue
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Abstract
The enterovirus echovirus 9 strain Barty (E9/Barty) is pathogenic for newborn mice as well as for humans. In contrast to the apathogenic prototype strain Hill, strain Barty encodes an RGD motif in the C-terminal part of the structural protein VP1. Data are presented that show that E9/Barty binds its target cells via contact of the RGD motif to the αvß3 integrin (vitronectin receptor), whereas prototype Hill uses a different, still unidentified receptor site. Furthermore, virus titres of murine muscle tissue were compared after infection of newborn and 1-, 2-, 3- and 12-week-old mice. The replication capacity of the virus decreased dramatically with age of the infected mice. Since E9/Barty does not replicate or replicates only poorly in mice older than about 5 days, and expression of the vitronectin receptor is reported to be down-regulated in striated muscle tissue during development, it is suggested that susceptibility of mice to this echovirus infection is controlled by the availability of αvß3 integrin.