UNDERSTANDING THE MECHANISMS INVOLVED IN ENTEROVIRUS 71 NEUROVIRULENCE

Abstract

Enterovirus A-71 (EV-A71) is one of the causative agents of hand, foot and mouth disease (HFMD) that is associated with neurological complications. In this work, ten EV-A71 clinical isolates of various genotypes were plaque-purified, and the growth kinetics was determined in vitro using human intestinal (Caco-2), muscle (RD), and neuronal (SH-SY5Y) cell lines that represented the main replication sites of the virus in its human host. Furthermore, the in vivo fitness and neurotropism of the isolates were studied in the 2-week-old AG129 mouse model. This work led to the identification of a neurotropic strain (N75) purified from a non-neurotropic clinical isolate (C2). Amino acid differences between N75 and C2 includes K149I in the structural VP2 protein that was previously found to be critical for neuroinvasion in AG129 mice. Other amino acid differences within the capsid VP1 protein and the RNA-dependent RNA polymerase could be potential determinants of neurovirulence.