A strain-specific epitope of enterovirus 71 identified by cryo-electron microscopy of the complex with fab from neutralizing antibody.
Enterovirus 71 (EV71) is a picornavirus that causes outbreaks of hand, foot, and mouth disease (HFMD), primarily in the Asia-Pacific area. Unlike coxsackievirus A16, which also causes HFMD, EV71 induces severe neuropathology leading to high fatalities, especially among children under the age of 6 years. Currently, no established vaccines or treatments are available against EV71 infection. The monoclonal antibody MA28-7 neutralizes only specific strains of EV71 that have a conserved glycine at amino acid VP1-145, a surface-exposed residue that maps to the 5-fold vertex and that has been implicated in receptor binding. The cryo-electron microscopy structure of a complex between EV71 and the Fab fragment of MA28-7 shows that only one Fab fragment occupies each 5-fold vertex. A positively charged patch, which has also been implicated in receptor binding, lies within the Fab footprint. We identify the strain-specific epitope of EV71 and discuss the possible neutralization mechanisms of the antibody.
Department of Medicine, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
Hyunwook
H
Lee
Javier O
JO
Cifuente
Robert E
RE
Ashley
James F
JF
Conway
Alexander M
AM
Makhov
Yoshio
Y
Tano
Hiroyuki
H
Shimizu
Yorihiro
Y
Nishimura
Susan
S
Hafenstein
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000648:ultrastructure; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000648:ultrastructure; D002675:Child, Preschool; D020285:Cryoelectron Microscopy; D029821:Enterovirus A, Human / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D014771:Virion / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments