A strain-specific epitope of enterovirus 71 identified by cryo-electron microscopy of the complex with fab from neutralizing antibody

Hyunwook Lee, Javier O. Cifuente, Robert E. Ashley, James F. Conway, Alexander M. Makhov, Yoshio Tano, Hiroyuki Shimizu, Yorihiro Nishimura, Susan Hafenstein

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37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11363-11370
Number of pages8
JournalJournal of virology
Volume87
Issue number21
DOIs
StatePublished - Oct 25 2013

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Lee, H., Cifuente, J. O., Ashley, R. E., Conway, J. F., Makhov, A. M., Tano, Y., Shimizu, H., Nishimura, Y., & Hafenstein, S. (2013). A strain-specific epitope of enterovirus 71 identified by cryo-electron microscopy of the complex with fab from neutralizing antibody. Journal of virology, 87(21), 11363-11370. https://doi.org/10.1128/JVI.01926-13