TY - JOUR
T1 - Theoretical analysis of the neuraminidase epitope of the Mexican A H1N1 influenza strain, and experimental studies on its interaction with rabbit and human hosts
AU - Loyola, Paola Kinara Reyes
AU - Campos-Rodríguez, R.
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
N1 - Funding Information:
Acknowledgments The authors thank ICyTDF (PIRIVE09-9), CONACYT, and PIFI-SIP-COFAA/IPN for financial support and Teresita Rocio Cruz for technical support. We are grateful to Bruce Allan Larsen for reviewing the use of English. Veronica Briz was supported by the Fondo de Investigación Sanitaria (Spain) through the Sara Borrell program (CD9/00433). MB and LTL thank CONACYT for scholarships.
PY - 2013/5
Y1 - 2013/5
N2 - 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.
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.
KW - Docking
KW - Epitope vaccine
KW - Influenza AH1N1
KW - Molecular dynamics simulations
KW - Neuraminidase
KW - Prediction of immunogenic epitopes
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U2 - 10.1007/s12026-013-8385-z
DO - 10.1007/s12026-013-8385-z
M3 - Article
C2 - 23371837
AN - SCOPUS:84876414055
SN - 0257-277X
VL - 56
SP - 44
EP - 60
JO - Immunologic Research
JF - Immunologic Research
IS - 1
ER -