Cargando…
Changed epitopes drive the antigenic drift for influenza A (H3N2) viruses
BACKGROUND: In circulating influenza viruses, gradually accumulated mutations on the glycoprotein hemagglutinin (HA), which interacts with infectivity-neutralizing antibodies, lead to the escape of immune system (called antigenic drift). The antibody recognition is highly correlated to the conformat...
Autores principales: | , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044287/ https://www.ncbi.nlm.nih.gov/pubmed/21342562 http://dx.doi.org/10.1186/1471-2105-12-S1-S31 |
_version_ | 1782198711446667264 |
---|---|
author | Huang, Jhang-Wei Yang, Jinn-Moon |
author_facet | Huang, Jhang-Wei Yang, Jinn-Moon |
author_sort | Huang, Jhang-Wei |
collection | PubMed |
description | BACKGROUND: In circulating influenza viruses, gradually accumulated mutations on the glycoprotein hemagglutinin (HA), which interacts with infectivity-neutralizing antibodies, lead to the escape of immune system (called antigenic drift). The antibody recognition is highly correlated to the conformation change on the antigenic sites (epitopes), which locate on HA surface. To quantify a changed epitope for escaping from neutralizing antibodies is the basis for the antigenic drift and vaccine development. RESULTS: We have developed an epitope-based method to identify the antigenic drift of influenza A utilizing the conformation changes on epitopes. A changed epitope, an antigenic site on HA with an accumulated conformation change to escape from neutralizing antibody, can be considered as a "key feature" for representing the antigenic drift. According to hemagglutination inhibition (HI) assays and HA/antibody complex structures, we statistically measured the conformation change of an epitope by considering the number of critical position mutations with high genetic diversity and antigenic scores. Experimental results show that two critical position mutations can induce the conformation change of an epitope to escape from the antibody recognition. Among five epitopes of HA, epitopes A and B, which are near to the receptor binding site, play a key role for neutralizing antibodies. In addition, two changed epitopes often drive the antigenic drift and can explain the selections of 24 WHO vaccine strains. CONCLUSIONS: Our method is able to quantify the changed epitopes on HA for predicting the antigenic variants and providing biological insights to the vaccine updates. We believe that our method is robust and useful for studying influenza virus evolution and vaccine development. |
format | Text |
id | pubmed-3044287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30442872011-02-25 Changed epitopes drive the antigenic drift for influenza A (H3N2) viruses Huang, Jhang-Wei Yang, Jinn-Moon BMC Bioinformatics Research BACKGROUND: In circulating influenza viruses, gradually accumulated mutations on the glycoprotein hemagglutinin (HA), which interacts with infectivity-neutralizing antibodies, lead to the escape of immune system (called antigenic drift). The antibody recognition is highly correlated to the conformation change on the antigenic sites (epitopes), which locate on HA surface. To quantify a changed epitope for escaping from neutralizing antibodies is the basis for the antigenic drift and vaccine development. RESULTS: We have developed an epitope-based method to identify the antigenic drift of influenza A utilizing the conformation changes on epitopes. A changed epitope, an antigenic site on HA with an accumulated conformation change to escape from neutralizing antibody, can be considered as a "key feature" for representing the antigenic drift. According to hemagglutination inhibition (HI) assays and HA/antibody complex structures, we statistically measured the conformation change of an epitope by considering the number of critical position mutations with high genetic diversity and antigenic scores. Experimental results show that two critical position mutations can induce the conformation change of an epitope to escape from the antibody recognition. Among five epitopes of HA, epitopes A and B, which are near to the receptor binding site, play a key role for neutralizing antibodies. In addition, two changed epitopes often drive the antigenic drift and can explain the selections of 24 WHO vaccine strains. CONCLUSIONS: Our method is able to quantify the changed epitopes on HA for predicting the antigenic variants and providing biological insights to the vaccine updates. We believe that our method is robust and useful for studying influenza virus evolution and vaccine development. BioMed Central 2011-02-15 /pmc/articles/PMC3044287/ /pubmed/21342562 http://dx.doi.org/10.1186/1471-2105-12-S1-S31 Text en Copyright ©2011 Huang and Yang; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Huang, Jhang-Wei Yang, Jinn-Moon Changed epitopes drive the antigenic drift for influenza A (H3N2) viruses |
title | Changed epitopes drive the antigenic drift for influenza A (H3N2) viruses |
title_full | Changed epitopes drive the antigenic drift for influenza A (H3N2) viruses |
title_fullStr | Changed epitopes drive the antigenic drift for influenza A (H3N2) viruses |
title_full_unstemmed | Changed epitopes drive the antigenic drift for influenza A (H3N2) viruses |
title_short | Changed epitopes drive the antigenic drift for influenza A (H3N2) viruses |
title_sort | changed epitopes drive the antigenic drift for influenza a (h3n2) viruses |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044287/ https://www.ncbi.nlm.nih.gov/pubmed/21342562 http://dx.doi.org/10.1186/1471-2105-12-S1-S31 |
work_keys_str_mv | AT huangjhangwei changedepitopesdrivetheantigenicdriftforinfluenzaah3n2viruses AT yangjinnmoon changedepitopesdrivetheantigenicdriftforinfluenzaah3n2viruses |