Fas receptor binding is a key determinant of the enhanced aggressiveness of the novel recombinant Echovirus 11.

A novel recombinant strain of Echovirus 11 has recently emerged worldwide and has been associated with increased pathogenicity, particularly causing severe disease in neonates. The enhanced virulence of this variant may be linked to its recombinant nature and the accumulation of mutations in capsid proteins.In this study, we investigated the relationship between genetic variations and virulence using a clinical isolate of the dominant Echovirus 11 D5 genotype, in comparison with the prototype strain. In vitro characterization in A549 human lung epithelial cells revealed that the clinical isolate exhibits significantly greater cytopathic effects than the prototype, as evidenced by increased lytic replication, reduced cell viability, and higher viral loads accompanied by enhanced release of infectious particles. The isolated virus was found to directly bind and activate the Fas receptor as demonstrated by surface plasmon resonance and cross-linking mass spectrometry analyses. This was found to enhance productive viral replication and facilitate the efficient release of newly assembled virions from infected cells, thereby promoting rapid viral dissemination. Collectively, these findings elucidate the mechanism underlying the increased aggressiveness of this emerging Echovirus 11 variant and underscore the importance of heightened surveillance and awareness of its potential clinical impact.