Seroproteomics Reveals Cross-reactivity of Anti-Enterovirus 71 Antibodies with Cytoplasmic Actin

Antibodies generated against Enterovirus 71 (EV71), the major etiological agent for Hand Foot and Mouth Disease (HFMD), were reported to cross-react with other enteroviruses and host proteins. Coxsackieviruses, which is serologically similar to EV71, was reported to mimic actin. Therefore, we hypothesized and successfully demonstrated the cross-reactivity of anti-EV71 antibody to cytoplasmic β-actin using seroproteomics approach. Using 3-dimensional modelling, the cross-reactivity might be due to the structural similarity between the previously reported immunodominant VP1 linear epitope and a homologous motif of cytoplasmic β-actin. Protein-protein docking simulation revealed a large surface of EV71 VP1 was able to bind to a region of the myosin VI cargo binding domain overlapping the cargo binding site. Myosin molecules was also identified to be co-precipitated with EV71 VP1, suggesting the possibility of EV71 VP1 to exploit its similarities to cytoplasmic β-actin so as to bind to myosin for viral shuttling in host cell. Our findings that antibodies against EV71 VP1 cross-react with cytoplasmic β-actin led us to proposed that EV71 may exploit the actin-myosin transport machinery for viral transport in host cells. Further experiments on the interaction of EV71 VP1 with cytoplasmic β-actin and myosin VI may elucidate the mechanism of EV71 infection.