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Molecular basis for serological cross-reactivity between enteroviruses
A Samuelson1, M Forsgren, B Johansson
1Department of Immunology, Microbiology, Pathology and Infectious Diseases, Huddinge Hospital, Sweden.
Abstract:
The recognition sites for human antibodies which are cross-reactive between different types of enteroviruses were determined and characterized. Serum samples obtained from 58 patients with culture-confirmed enteroviral infections were analyzed in enzyme immunoassays against two sets of overlapping synthetic peptides covering residues 31 to 96 of poliovirus 1 VP1 (Mahoney strain) and residues 31 to 148 of coxsackievirus B1 VP1 (position based on alignment with poliovirus 1 VP1, Mahoney strain). A major antigenic region eliciting cross-reactive antibodies could be located to residues 37 to 51 of VP1. Furthermore, a single peptide covering residues 42 to 55 almost completely inhibited the binding of human antibodies to heat-inactivated enteroviruses, indicating that residues 42 to 55 of VP1 contain a major region eliciting cross-reactive antibodies. By using peptide analogs in which each residue within positions 42 to 55 of VP1 was sequentially substituted by Ala or Gly, we were able to determine the most essential residues for human antibody binding in 38 of the convalescent-phase patient serum samples. In a majority of the serum samples, the most essential residues for antibody binding were found to be Pro-42, Ala-43, Leu-44, Thr-45, Ala-46, Glu-48, Thr-49, and Gly-50. All of these residues are conserved, according to known enterovirus sequences, with the divergent echovirus 22 excepted. In conclusion, we could demonstrate that the essential residues for binding of cross-reactive antibodies are well conserved within the enterovirus family. These findings provide a molecular basis for the observed antibody cross-reactivity within the enterovirus group.
Insights
Human antibodies cross-reacting between enteroviruses target conserved VP1 protein residues 42-55. This finding explains antibody cross-reactivity and provides a molecular basis for enterovirus immunity.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Enteroviruses are a significant cause of human disease.
- Antibody cross-reactivity between different enteroviruses is a known phenomenon.
- The specific recognition sites responsible for this cross-reactivity have not been fully characterized.
Purpose of the Study:
- To determine and characterize the recognition sites for human antibodies that cross-react between different enteroviruses.
- To identify the specific amino acid residues within the viral capsid protein VP1 that are critical for this cross-reactivity.
Main Methods:
- Enzyme immunoassays were performed using serum samples from patients with enteroviral infections.
- Overlapping synthetic peptides covering regions of poliovirus 1 VP1 and coxsackievirus B1 VP1 were used.
- Peptide analogs with specific residue substitutions were employed to pinpoint essential amino acids.
Main Results:
- A major antigenic region eliciting cross-reactive antibodies was located to residues 37-51 of VP1.
- A peptide spanning residues 42-55 of VP1 significantly inhibited antibody binding.
- Specific residues (Pro-42, Ala-43, Leu-44, Thr-45, Ala-46, Glu-48, Thr-49, Gly-50) within this region were identified as essential for antibody binding.
Conclusions:
- The essential residues for binding of cross-reactive antibodies are highly conserved within the enterovirus family, with notable exceptions like echovirus 22.
- These findings provide a molecular basis for understanding enterovirus antibody cross-reactivity.
- This knowledge can inform the development of broader-acting antiviral strategies.