The Role of VP1 Amino Acid Residue 145 of Enterovirus 71 in Viral Fitness and Pathogenesis in a Cynomolgus Monkey Model

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Recently, large outbreaks of hand, foot, and mouth disease, including fatal neurological cases in young children primarily because of enterovirus 71 (EV71) have been reported, particularly in the Asia Pacific regions where the disease poses a serious threat to public health. Based on mutational and structural analyses of EV71, we identified amino acid residue 145 of the capsid protein VP1 (VP1-145) as a critical molecular determinant for the binding of EV71 to a specific cellular receptor, human P-selectin glycoprotein ligand-1 (PSGL-1). VP1-145 is highly variable among EV71 isolates and has been identified as a potential neurovirulence determinant in humans and experimental mouse models. To elucidate the in vivo involvement of PSGL-1-depentent replication and pathogenesis, we investigated viral replication, genetic stability, and the pathogenicity of the PSGL-1-binding (PB) and PSGL-1-nonbinding (non-PB) strains of EV71 in a cynomolgus monkey model. After the intravenous inoculation with the PB strain, viruses found to be highly mutated at VP1-145 with resultant VP1-145E variants (non-PB) inducing viremia and neuropathogenesis, presumably in a PSGL-1-independent manner. VP1-145G variants were identified only in peripheral blood mononuclear cells from two PB-inoculated monkeys. Our study provides new insights into the interplay between virus, receptors, and host in EV71-infected individuals.

Vyšlo v časopise: The Role of VP1 Amino Acid Residue 145 of Enterovirus 71 in Viral Fitness and Pathogenesis in a Cynomolgus Monkey Model. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005033
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005033

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