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Editor, Senior Moderator
PLoS One. 2014 Apr 3;9(4):e93632. doi: 10.1371/journal.pone.0093632. eCollection 2014.
Influenza A H1N1 Pandemic Strain Evolution - Divergence and the Potential for Antigenic Drift Variants.
Klein EY1, Serohijos AW2, Choi JM2, Shakhnovich EI2, Pekosz A3.
Author information
1Center for Advanced Modeling in the Social, Behavioral, and Health Sciences, Department of Emergency Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America; Center for Disease Dynamics, Economics, and Policy, Washington, DC, United States of America.
2Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America.
3W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
Abstract
The emergence of a novel A(H1N1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. We examined changes in the nucleotide coding regions and the amino acid sequences of the hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) segments of the A(H1N1)pdm09 strain using publicly available data. We calculated the nucleotide and amino acid hamming distance from the vaccine strain A/California/07/2009 for each sequence. We also estimated Pepitope-a measure of antigenic diversity based on changes in the epitope regions-for each isolate. Finally, we compared our results to A(H3N2) strains collected over the same period. Our analysis found that the mean hamming distance for the HA protein of the A(H1N1)pdm09 strain increased from 3.6 (standard deviation [SD]: 1.3) in 2009 to 11.7 (SD: 1.0) in 2013, while the mean hamming distance in the coding region increased from 7.4 (SD: 2.2) in 2009 to 28.3 (SD: 2.1) in 2013. These trends are broadly similar to the rate of mutation in H3N2 over the same time period. However, in contrast to H3N2 strains, the rate of mutation accumulation has slowed in recent years. Our results are notable because, over the course of the study, mutation rates in H3N2 similar to that seen with A(H1N1)pdm09 led to the emergence of two antigenic drift variants. However, while there has been an H1N1 epidemic in North America this season, evidence to date indicates the vaccine is still effective, suggesting the epidemic is not due to the emergence of an antigenic drift variant. Our results suggest that more research is needed to understand how viral mutations are related to vaccine effectiveness so that future vaccine choices and development can be more predictive.
PMID:
24699432
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24699432
Influenza A H1N1 Pandemic Strain Evolution - Divergence and the Potential for Antigenic Drift Variants.
Klein EY1, Serohijos AW2, Choi JM2, Shakhnovich EI2, Pekosz A3.
Author information
1Center for Advanced Modeling in the Social, Behavioral, and Health Sciences, Department of Emergency Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America; Center for Disease Dynamics, Economics, and Policy, Washington, DC, United States of America.
2Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America.
3W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
Abstract
The emergence of a novel A(H1N1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. We examined changes in the nucleotide coding regions and the amino acid sequences of the hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) segments of the A(H1N1)pdm09 strain using publicly available data. We calculated the nucleotide and amino acid hamming distance from the vaccine strain A/California/07/2009 for each sequence. We also estimated Pepitope-a measure of antigenic diversity based on changes in the epitope regions-for each isolate. Finally, we compared our results to A(H3N2) strains collected over the same period. Our analysis found that the mean hamming distance for the HA protein of the A(H1N1)pdm09 strain increased from 3.6 (standard deviation [SD]: 1.3) in 2009 to 11.7 (SD: 1.0) in 2013, while the mean hamming distance in the coding region increased from 7.4 (SD: 2.2) in 2009 to 28.3 (SD: 2.1) in 2013. These trends are broadly similar to the rate of mutation in H3N2 over the same time period. However, in contrast to H3N2 strains, the rate of mutation accumulation has slowed in recent years. Our results are notable because, over the course of the study, mutation rates in H3N2 similar to that seen with A(H1N1)pdm09 led to the emergence of two antigenic drift variants. However, while there has been an H1N1 epidemic in North America this season, evidence to date indicates the vaccine is still effective, suggesting the epidemic is not due to the emergence of an antigenic drift variant. Our results suggest that more research is needed to understand how viral mutations are related to vaccine effectiveness so that future vaccine choices and development can be more predictive.
PMID:
24699432
[PubMed - in process]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/24699432