Giuseppe
Emeritus
[Source: PLoS ONE, full text: (LINK). Abstract, edited.]
Emerged HA and NA Mutants of the Pandemic Influenza H1N1 Viruses with Increasing Epidemiological Significance in Taipei and Kaohsiung, Taiwan, 2009?10
Chuan-Liang Kao<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP><SUP>,</SUP><SUP>3</SUP>, Ta-Chien Chan<SUP>1</SUP>, Chu-Han Tsai<SUP>2</SUP>, Kuan-Ying Chu<SUP>1</SUP>, Shu-Fang Chuang<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP>, Chang-Chun Lee<SUP>1</SUP>, Zheng-Rong Tiger Li<SUP>1</SUP>, Ko-Wen Wu<SUP>5</SUP>, Luan-Yin Chang<SUP>4</SUP>, Yea-Huei Shen<SUP>6</SUP>, Li-Min Huang<SUP>4</SUP>, Ping-Ing Lee<SUP>4</SUP>, ChingLai Yang<SUP>7</SUP>, Richard Compans<SUP>7</SUP>, Barry T. Rouse<SUP>8</SUP>, Chwan-Chuen King<SUP>1</SUP><SUP>*</SUP>
1 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University (NTU), Taipei, Taiwan, Republic of China (ROC), 2 Department of Clinical Laboratory Sciences & Medical Biotechnology, College of Medicine, NTU, Taipei, Taiwan, Republic of China (ROC), 3 Department of Laboratory Medicine, NTU Hospital, Taipei, Taiwan, Republic of China (ROC), 4 Department of Pediatrics, NTU Hospital, Taipei, Taiwan, Republic of China (ROC), 5 Institute of Biomedical Informatics, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan, Republic of China (ROC), 6 Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan, Republic of China (ROC), 7 Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America, 8 Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee, United States of America
Abstract
The 2009 influenza pandemic provided an opportunity to observe dynamic changes of the hemagglutinin (HA) and neuraminidase (NA) of pH1N1 strains that spread in two metropolitan areas -Taipei and Kaohsiung. We observed cumulative increases of amino acid substitutions of both HA and NA that were higher in the post?peak than in the pre-peak period of the epidemic. About 14.94% and 3.44% of 174 isolates had one and two amino acids changes, respective, in the four antigenic sites. One unique adaptive mutation of HA2 (E374K) was first detected three weeks before the epidemic peak. This mutation evolved through the epidemic, and finally emerged as the major circulated strain, with significantly higher frequency in the post-peak period than in the pre-peak (64.65% vs 9.28%, p<0.0001). E374K persisted until ten months post-nationwide vaccination without further antigenic changes (e.g. prior to the highest selective pressure). In public health measures, the epidemic peaked at seven weeks after oseltamivir treatment was initiated. The emerging E374K mutants spread before the first peak of school class suspension, extended their survival in high-density population areas before vaccination, dominated in the second wave of class suspension, and were fixed as herd immunity developed. The tempo-spatial spreading of E374K mutants was more concentrated during the post?peak (p = 0.000004) in seven districts with higher spatial clusters (p<0.001). This is the first study examining viral changes during the na?ve phase of a pandemic of influenza through integrated virological/serological/clinical surveillance, tempo-spatial analysis, and intervention policies. The vaccination increased the percentage of E374K mutants (22.86% vs 72.34%, p<0.001) and significantly elevated the frequency of mutations in Sa antigenic site (2.36% vs 23.40%, p<0.001). Future pre-vaccination public health efforts should monitor amino acids of HA and NA of pandemic influenza viruses isolated at exponential and peak phases in areas with high cluster cases.
Citation: Kao C-L, Chan T-C, Tsai C-H, Chu K-Y, Chuang S-F, et al. (2012) Emerged HA and NA Mutants of the Pandemic Influenza H1N1 Viruses with Increasing Epidemiological Significance in Taipei and Kaohsiung, Taiwan, 2009?10. PLoS ONE 7(2): e31162. doi:10.1371/journal.pone.0031162
Editor: Jianming Tang, University of Alabama at Birmingham, United States of America
Received: October 21, 2011; Accepted: January 3, 2012; Published: February 6, 2012
Copyright: ? 2012 Kao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research was supported by three grants: NSC #98-2321-B-002-016 from Taiwan's National Science Council, and financial support from the National Institutes of Health in the United States (NIH grant #2U19AI05726606 and NIH grant #HHSN266200700006C). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: chwanchuen@gmail.com
- ------Chuan-Liang Kao<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP><SUP>,</SUP><SUP>3</SUP>, Ta-Chien Chan<SUP>1</SUP>, Chu-Han Tsai<SUP>2</SUP>, Kuan-Ying Chu<SUP>1</SUP>, Shu-Fang Chuang<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP>, Chang-Chun Lee<SUP>1</SUP>, Zheng-Rong Tiger Li<SUP>1</SUP>, Ko-Wen Wu<SUP>5</SUP>, Luan-Yin Chang<SUP>4</SUP>, Yea-Huei Shen<SUP>6</SUP>, Li-Min Huang<SUP>4</SUP>, Ping-Ing Lee<SUP>4</SUP>, ChingLai Yang<SUP>7</SUP>, Richard Compans<SUP>7</SUP>, Barry T. Rouse<SUP>8</SUP>, Chwan-Chuen King<SUP>1</SUP><SUP>*</SUP>
1 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University (NTU), Taipei, Taiwan, Republic of China (ROC), 2 Department of Clinical Laboratory Sciences & Medical Biotechnology, College of Medicine, NTU, Taipei, Taiwan, Republic of China (ROC), 3 Department of Laboratory Medicine, NTU Hospital, Taipei, Taiwan, Republic of China (ROC), 4 Department of Pediatrics, NTU Hospital, Taipei, Taiwan, Republic of China (ROC), 5 Institute of Biomedical Informatics, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan, Republic of China (ROC), 6 Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan, Republic of China (ROC), 7 Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America, 8 Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee, United States of America
Abstract
The 2009 influenza pandemic provided an opportunity to observe dynamic changes of the hemagglutinin (HA) and neuraminidase (NA) of pH1N1 strains that spread in two metropolitan areas -Taipei and Kaohsiung. We observed cumulative increases of amino acid substitutions of both HA and NA that were higher in the post?peak than in the pre-peak period of the epidemic. About 14.94% and 3.44% of 174 isolates had one and two amino acids changes, respective, in the four antigenic sites. One unique adaptive mutation of HA2 (E374K) was first detected three weeks before the epidemic peak. This mutation evolved through the epidemic, and finally emerged as the major circulated strain, with significantly higher frequency in the post-peak period than in the pre-peak (64.65% vs 9.28%, p<0.0001). E374K persisted until ten months post-nationwide vaccination without further antigenic changes (e.g. prior to the highest selective pressure). In public health measures, the epidemic peaked at seven weeks after oseltamivir treatment was initiated. The emerging E374K mutants spread before the first peak of school class suspension, extended their survival in high-density population areas before vaccination, dominated in the second wave of class suspension, and were fixed as herd immunity developed. The tempo-spatial spreading of E374K mutants was more concentrated during the post?peak (p = 0.000004) in seven districts with higher spatial clusters (p<0.001). This is the first study examining viral changes during the na?ve phase of a pandemic of influenza through integrated virological/serological/clinical surveillance, tempo-spatial analysis, and intervention policies. The vaccination increased the percentage of E374K mutants (22.86% vs 72.34%, p<0.001) and significantly elevated the frequency of mutations in Sa antigenic site (2.36% vs 23.40%, p<0.001). Future pre-vaccination public health efforts should monitor amino acids of HA and NA of pandemic influenza viruses isolated at exponential and peak phases in areas with high cluster cases.
Citation: Kao C-L, Chan T-C, Tsai C-H, Chu K-Y, Chuang S-F, et al. (2012) Emerged HA and NA Mutants of the Pandemic Influenza H1N1 Viruses with Increasing Epidemiological Significance in Taipei and Kaohsiung, Taiwan, 2009?10. PLoS ONE 7(2): e31162. doi:10.1371/journal.pone.0031162
Editor: Jianming Tang, University of Alabama at Birmingham, United States of America
Received: October 21, 2011; Accepted: January 3, 2012; Published: February 6, 2012
Copyright: ? 2012 Kao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research was supported by three grants: NSC #98-2321-B-002-016 from Taiwan's National Science Council, and financial support from the National Institutes of Health in the United States (NIH grant #2U19AI05726606 and NIH grant #HHSN266200700006C). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: chwanchuen@gmail.com