Emerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009-10.

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 highe...

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Autores principales:	Chuan-Liang Kao, Ta-Chien Chan, Chu-Han Tsai, Kuan-Ying Chu, Shu-Fang Chuang, Chang-Chun Lee, Zheng-Rong Tiger Li, Ko-Wen Wu, Luan-Yin Chang, Yea-Huei Shen, Li-Min Huang, Ping-Ing Lee, Chinglai Yang, Richard Compans, Barry T Rouse, Chwan-Chuen King
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7a394ad3300a4acdba3f2d06f99b734f
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spelling	oai:doaj.org-article:7a394ad3300a4acdba3f2d06f99b734f2021-11-18T07:28:49ZEmerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009-10.1932-620310.1371/journal.pone.0031162https://doaj.org/article/7a394ad3300a4acdba3f2d06f99b734f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22328930/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The 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 naïve 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.Chuan-Liang KaoTa-Chien ChanChu-Han TsaiKuan-Ying ChuShu-Fang ChuangChang-Chun LeeZheng-Rong Tiger LiKo-Wen WuLuan-Yin ChangYea-Huei ShenLi-Min HuangPing-Ing LeeChinglai YangRichard CompansBarry T RouseChwan-Chuen KingPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31162 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chuan-Liang Kao Ta-Chien Chan Chu-Han Tsai Kuan-Ying Chu Shu-Fang Chuang Chang-Chun Lee Zheng-Rong Tiger Li Ko-Wen Wu Luan-Yin Chang Yea-Huei Shen Li-Min Huang Ping-Ing Lee Chinglai Yang Richard Compans Barry T Rouse Chwan-Chuen King Emerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009-10.
description	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 naïve 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.
format	article
author	Chuan-Liang Kao Ta-Chien Chan Chu-Han Tsai Kuan-Ying Chu Shu-Fang Chuang Chang-Chun Lee Zheng-Rong Tiger Li Ko-Wen Wu Luan-Yin Chang Yea-Huei Shen Li-Min Huang Ping-Ing Lee Chinglai Yang Richard Compans Barry T Rouse Chwan-Chuen King
author_facet	Chuan-Liang Kao Ta-Chien Chan Chu-Han Tsai Kuan-Ying Chu Shu-Fang Chuang Chang-Chun Lee Zheng-Rong Tiger Li Ko-Wen Wu Luan-Yin Chang Yea-Huei Shen Li-Min Huang Ping-Ing Lee Chinglai Yang Richard Compans Barry T Rouse Chwan-Chuen King
author_sort	Chuan-Liang Kao
title	Emerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009-10.
title_short	Emerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009-10.
title_full	Emerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009-10.
title_fullStr	Emerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009-10.
title_full_unstemmed	Emerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009-10.
title_sort	emerged ha and na mutants of the pandemic influenza h1n1 viruses with increasing epidemiological significance in taipei and kaohsiung, taiwan, 2009-10.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/7a394ad3300a4acdba3f2d06f99b734f
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Emerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009-10.

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