Molecular basis of differential receptor usage for naturally occurring CD55-binding and -nonbinding coxsackievirus B3 strains

Abstract

Significance Receptor usage can affect cell tropism and viral pathogenicity. CVB causes viral-induced heart disease, aseptic meningitis, and many other severe diseases globally that can engage CAR in host cells and selectively utilizes CD55 to infect them. However, the mechanism of CVB differential receptor usage and its dynamic entry into cells remains poorly understood. This study elucidates the molecular mechanism of VP3-234 residues as critical population selection determinants influencing CD55 affinity/specificity for naturally occurring CVB3 strains. Moreover, the demonstration that CAR facilitates viral uncoating with strain-dependent pH preferences suggests that the entry and infection of different enterovirus strains vary with the extent of pH dependence. Altogether, these findings expand our understanding of nonenveloped virus infections and provide clues for therapeutic interventions.