Decoding the complex receptor landscape of enterovirus D68

Enterovirus D68 (EV-D68) is an emerging pathogen associated with severe respiratory diseases and central nervous system complications. This pearl summarizes the roles of glycan receptors, such as sialic acid, and protein receptors like ICAM-5 and MFSD6 in EV-D68 infection. MFSD6 serves as a primary receptor due to its widespread distribution in tissues, while sialic acid and ICAM-5 play a synergistic role in facilitating invasion across various tissues. We have elaborated on the correlation between receptor distribution, tissue tropism, and pathogenicity. The complex receptor system of EV-D68 enhances its pathogenicity by facilitating multi-tissue invasion and allowing the virus to adapt to various microenvironments. This adaptability provides insights into distinct receptor preferences and their associations with pathogenic outcomes, where specific receptor binding can influence the severity of infection. Additionally, we discuss the effectiveness of receptor-targeted inhibitors and the potential for therapeutic interventions aimed at disrupting receptor-virus interactions. Our pearl underscores the multifaceted nature of EV-D68 receptors and their implications for the development of novel antiviral strategies.