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Identification and characterization of neutralization epitopes at VP2 and VP1 of enterovirus A71

Nmn NikNadia1, Chee Wah Tan1, Kien Chai Ong2

  • 1Faculty of Medicine, Department of Medical Microbiology, University of Malaya, Kuala Lumpur, Malaysia.

Journal of Medical Virology
|February 20, 2018
PubMed

Insights

Enterovirus A71 (EV-A71) escape mutants revealed VP1-14 as crucial for acute human infection, particularly its recognition of IgM. This N-terminus VP1 region shows promise for developing diagnostics and therapeutics against EV-A71.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Enterovirus A71 (EV-A71) is a significant human pathogen causing hand, foot, and mouth disease and severe neurological complications.
  • Neutralizing antibodies are critical for controlling EV-A71 infections, but the virus can evolve escape mutants.
  • Understanding the mechanisms of EV-A71 immune escape is essential for developing effective vaccines and therapies.

Purpose of the Study:

  • To identify and characterize EV-A71 neutralization escape mutants generated against a specific monoclonal antibody.
  • To investigate the functional significance of identified mutations in viral neutralization and infectivity.
  • To evaluate the potential of viral epitopes as targets for diagnostics and therapeutics.

Main Methods:

  • Generation of EV-A71 neutralization escape mutants using monoclonal antibody MAB979.
  • Identification of amino acid substitutions in viral proteins (VP2 and VP1) through sequencing.
  • Construction of infectious EV-A71 clones harboring specific mutations using reverse genetics.
  • Neutralization assays using immune sera from infected mice and humans.

Main Results:

  • Two key substitutions, VP2-T141I and VP1-D14N, were identified in escape mutants.
  • The VP1-D14N substitution at the VP1 N-terminus was found to be more critical for neutralization escape in acute human infection compared to VP2-T141I.
  • The VP1 N-terminus demonstrated significant recognition of IgM antibodies present during acute infection.

Conclusions:

  • The N-terminus of EV-A71 VP1 is a critical determinant for neutralization escape, particularly due to its interaction with IgM during acute infection.
  • The identified VP1 N-terminus epitope represents a promising target for the development of novel diagnostics and therapeutic antibodies against EV-A71.
  • Further research into VP1 N-terminus-targeting strategies could lead to improved control of EV-A71 outbreaks.
Keywords:
capsidenterovirusenterovirus A71geneticshand, foot, and mouth diseaseimmune responsesmutationneutralization

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