Enterovirus A71 (EV-A71) is a major etiological agent of hand, foot and mouth disease (HFMD), infecting mainly children under the age of five. EV-A71 is transmitted via the faecal-oral route and usually manifests through fever and skin lesions. However, severe systemic infection can cause meningitis, encephalitis, and death.
Understanding EV-A71 systemic transmission has been challenging due to its ability to use several cellular receptors. Scavenger receptor B2 (SCARB2) plays a critical role in virion internalisation and is necessary for infection. Other receptors such as heparan sulfate (HS) and P-selectin glycoprotein ligand-1 (PSGL-1) play important receptor roles. Interestingly, sialic acid and sialylated glycans were recently indirectly observed to act as receptors for EV-A71. EV71 strains are often classified as PSGL-1 binding (PB) or non-PSGL-1 binding (non-PB). PB and non-PB strains differ in disease progression, severity, and outcome. Receptor binging ability and/or affinity have been linked to a few amino acids on the EV-A71 viral capsid protein 1 (VP1). It was recently demonstrated that passaging clinical isolates in standard permissive cell lines led to critical mutations of VP1, and influenced, among other things, the PB status of clinical isolates. This cell culture adaptation makes replicating and studying clinical isolates challenging and contributes to the difficulty of designing and evaluating virus binding inhibitors.
Our study aims to elucidate the underlying mechanisms of selection pressure in this context, complemented by a comprehensive proteomic analysis of infected cells using DIA mass spectrometry. This acquired knowledge will serve as a foundation to better comprehend the fluctuating effectiveness of specific compounds and play a pivotal role in the design of innovative antiviral treatments.