Theoretical analysis of the neuraminidase epitope of the Mexican A H1N1 influenza strain, and experimental studies on its interaction with rabbit and human hosts

Paola Kinara Reyes Loyola, R. Campos-Rodríguez, Martiniano Bello, S. Rojas-Hernández, Mirko Zimic, Miguel Quiliano, Verónica Briz, M. Angeles Muñoz-Fernández, Luis Tolentino-López, Jose Correa-Basurto

Research output: Contribution to journalArticle

Abstract

The neuraminidase (NA) epitope from the Mexican AH1N1 influenza virus was identified by using sequences registered at the GenBank during the peak of a pandemic (from April 2009 to October 2010). First, NA protein sequences were submitted for multiple alignment analysis, and their three-dimensional models (3-D) were then built by using homology modeling. The most common sequence (denominated wild-type) and its mutants were submitted to linear and nonlinear epitope predictors, which included the major histocompatibility complex type II (MHC II) and B-cell peptides. The epitope prediction was in accordance with evolutionary behavior and some protein structural properties. The latter included a low NA mutation rate, NA 3-D surface exposure, and the presence of high hindrance side chain residues. After selecting the epitope, docking studies and molecular dynamics (MD) simulations were used to explore interactions between the epitope and MHC II. Afterward, several experimental assays were performed to validate the theoretical study by using antibodies from humans (infected by pandemic H1N1) and rabbits (epitope vaccination). The results show 119 complete sequences that were grouped into 28 protein sequences according to their identity (one wild-type and 27 representative mutants (1-5 mutations)). The predictors yielded several epitopes, with the best fit being the one located in the C-terminal region. Theoretical methods demonstrated that the selected epitope reached the P4, P6, P7, and P9 pockets of MHC II, whereas the experimental evidence indicates that the epitope is recognized by human antibodies and also by rabbit antibodies immunized with the peptide.

Original languageEnglish (US)
Pages (from-to)44-60
Number of pages17
JournalImmunologic Research
Volume56
Issue number1
DOIs
StatePublished - May 2013
Externally publishedYes

Fingerprint

Neuraminidase
Human Influenza
Epitopes
Rabbits
Major Histocompatibility Complex
Pandemics
Antibodies
Peptides
Proteins
Nucleic Acid Databases
Mutation Rate
Molecular Dynamics Simulation
Orthomyxoviridae
Vaccination
B-Lymphocytes
Theoretical Models
Mutation

Keywords

  • Docking
  • Epitope vaccine
  • Influenza AH1N1
  • Molecular dynamics simulations
  • Neuraminidase
  • Prediction of immunogenic epitopes

ASJC Scopus subject areas

  • Immunology

Cite this

Theoretical analysis of the neuraminidase epitope of the Mexican A H1N1 influenza strain, and experimental studies on its interaction with rabbit and human hosts. / Loyola, Paola Kinara Reyes; Campos-Rodríguez, R.; Bello, Martiniano; Rojas-Hernández, S.; Zimic, Mirko; Quiliano, Miguel; Briz, Verónica; Muñoz-Fernández, M. Angeles; Tolentino-López, Luis; Correa-Basurto, Jose.

In: Immunologic Research, Vol. 56, No. 1, 05.2013, p. 44-60.

Research output: Contribution to journalArticle

Loyola, PKR, Campos-Rodríguez, R, Bello, M, Rojas-Hernández, S, Zimic, M, Quiliano, M, Briz, V, Muñoz-Fernández, MA, Tolentino-López, L & Correa-Basurto, J 2013, 'Theoretical analysis of the neuraminidase epitope of the Mexican A H1N1 influenza strain, and experimental studies on its interaction with rabbit and human hosts', Immunologic Research, vol. 56, no. 1, pp. 44-60. https://doi.org/10.1007/s12026-013-8385-z
Loyola, Paola Kinara Reyes ; Campos-Rodríguez, R. ; Bello, Martiniano ; Rojas-Hernández, S. ; Zimic, Mirko ; Quiliano, Miguel ; Briz, Verónica ; Muñoz-Fernández, M. Angeles ; Tolentino-López, Luis ; Correa-Basurto, Jose. / Theoretical analysis of the neuraminidase epitope of the Mexican A H1N1 influenza strain, and experimental studies on its interaction with rabbit and human hosts. In: Immunologic Research. 2013 ; Vol. 56, No. 1. pp. 44-60.
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AU - Bello, Martiniano

AU - Rojas-Hernández, S.

AU - Zimic, Mirko

AU - Quiliano, Miguel

AU - Briz, Verónica

AU - Muñoz-Fernández, M. Angeles

AU - Tolentino-López, Luis

AU - Correa-Basurto, Jose

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AB - The neuraminidase (NA) epitope from the Mexican AH1N1 influenza virus was identified by using sequences registered at the GenBank during the peak of a pandemic (from April 2009 to October 2010). First, NA protein sequences were submitted for multiple alignment analysis, and their three-dimensional models (3-D) were then built by using homology modeling. The most common sequence (denominated wild-type) and its mutants were submitted to linear and nonlinear epitope predictors, which included the major histocompatibility complex type II (MHC II) and B-cell peptides. The epitope prediction was in accordance with evolutionary behavior and some protein structural properties. The latter included a low NA mutation rate, NA 3-D surface exposure, and the presence of high hindrance side chain residues. After selecting the epitope, docking studies and molecular dynamics (MD) simulations were used to explore interactions between the epitope and MHC II. Afterward, several experimental assays were performed to validate the theoretical study by using antibodies from humans (infected by pandemic H1N1) and rabbits (epitope vaccination). The results show 119 complete sequences that were grouped into 28 protein sequences according to their identity (one wild-type and 27 representative mutants (1-5 mutations)). The predictors yielded several epitopes, with the best fit being the one located in the C-terminal region. Theoretical methods demonstrated that the selected epitope reached the P4, P6, P7, and P9 pockets of MHC II, whereas the experimental evidence indicates that the epitope is recognized by human antibodies and also by rabbit antibodies immunized with the peptide.

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