| Summary: | <p>Hand, foot and mouth disease (HFMD) is an infectious disease that mainly infects
infants and children and has caused epidemics widely in the Asia-Pacific region in the
last 20 years. Enterovirus 71 (EV71) is one of the most common causes of HFMD. HFMD caused by EV71 is sometimes quite harmful because EV71 can induce severe
cardiac or central nervous system (CNS) complications. </p>
<p>Although EV71 vaccines have been approved in China, there are no other effective
means to treat EV71 infection. Our collaborators have identified and characterized 13
human monoclonal antibodies (mAbs) that can neutralize EV71. Blocking EV71 entry
with therapeutic antibodies could be a new useful strategy. </p>
<p>Human scavenger receptor class B, member 2 (SCARB2) is a cellular receptor for
EV71 and can induce attachment and uncoating. SCARB2 is a key factor in the entry
process of EV71, however a structure of EV71-SCARB2 complex has not been
available to clarify EV71-SCARB2 interaction. </p>
<p>We have determined the cryo-EM structure of the EV71-SCARB2 complex. SCARB2
was found to bind outside the canyon region, different from the binding patterns of
many IgG-like picornavirus receptors. The VP1 GH and VP2 EF loops of the EV71
capsid, together with helices α5 and α7 of SCARB2, are involved in virus-receptor
interactions. </p>
<p>With anti-EV71 antibodies from our collaborators, we also solved Fab structures as
well as cryo-EM structures of EV71-Fab complexes. In these structures, the binding
sites of antibodies can be classified into three groups: canyon, 2-fold-axis area and 3-
fold-axis area. Antibodies that bind near the canyon region share some common
binding residues or have overlapped volume with SCARB2 when binding with EV71, so may use a receptor-blocking neutralization mechanism. Antibodies binding near the
2-fold axis may block genome release of EV71, since it is thought EV71 releases its
genome from the channel at the 2-fold axis. Antibodies binding near the 3-fold axis
slightly increase the stability of EV71 virions, which may also contribute to the
neutralization of EV71 by these antibodies. </p>
<p>Our studies on EV71-receptor interaction and neutralization mechanisms of antibodies
may contribute to the development of structure-based anti-EV71 drugs and antibody- based therapy for HFMD.</p>
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