A Strain-Specific Epitope of Enterovirus 71 Identified by Cryo-Electron Microscopy of the Complex with Fab from Neutralizing Antibody

Autor: Yoshio Tano, Javier O. Cifuente, Hiroyuki Shimizu, James F. Conway, Hyunwook Lee, Alexander M. Makhov, Robert E. Ashley, Yorihiro Nishimura, Susan Hafenstein
Rok vydání: 2013
Předmět:
Zdroj: Journal of Virology. 87:11363-11370
ISSN: 1098-5514
0022-538X
DOI: 10.1128/jvi.01926-13
Popis: 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.
Databáze: OpenAIRE