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Next-Generation Sequencing Analysis of the Within-Host Genetic Diversity of Influenza A(H1N1)pdm09 Viruses in the Upper and Lower Respiratory Tracts of Patients with Severe Influenza

The influenza A(H1N1)pdm09 virus emerged in April 2009 with an unusual incidence of severe disease and mortality, and currently circulates as a seasonal influenza virus. Previous studies using consensus viral genome sequencing data have overlooked the viral genomic and phenotypic diversity. Next-gen...

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Autores principales: Takayama, Ikuyo, Nguyen, Binh Gia, Dao, Co Xuan, Pham, Thach The, Dang, Tuan Quoc, Truong, Phuong Thai, Do, Thanh Van, Pham, Thuy Thi Phuong, Fujisaki, Seiichiro, Odagiri, Takato, Hasegawa, Hideki, Nakajima, Noriko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845592/
https://www.ncbi.nlm.nih.gov/pubmed/33408229
http://dx.doi.org/10.1128/mSphere.01043-20
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author Takayama, Ikuyo
Nguyen, Binh Gia
Dao, Co Xuan
Pham, Thach The
Dang, Tuan Quoc
Truong, Phuong Thai
Do, Thanh Van
Pham, Thuy Thi Phuong
Fujisaki, Seiichiro
Odagiri, Takato
Hasegawa, Hideki
Nakajima, Noriko
author_facet Takayama, Ikuyo
Nguyen, Binh Gia
Dao, Co Xuan
Pham, Thach The
Dang, Tuan Quoc
Truong, Phuong Thai
Do, Thanh Van
Pham, Thuy Thi Phuong
Fujisaki, Seiichiro
Odagiri, Takato
Hasegawa, Hideki
Nakajima, Noriko
author_sort Takayama, Ikuyo
collection PubMed
description The influenza A(H1N1)pdm09 virus emerged in April 2009 with an unusual incidence of severe disease and mortality, and currently circulates as a seasonal influenza virus. Previous studies using consensus viral genome sequencing data have overlooked the viral genomic and phenotypic diversity. Next-generation sequencing (NGS) may instead be used to characterize viral populations in an unbiased manner and to measure within-host genetic diversity. In this study, we used NGS analysis to investigate the within-host genetic diversity of influenza A(H1N1)pdm09 virus in the upper and lower respiratory samples from nine patients who were admitted to the intensive care unit (ICU). A total of 47 amino acid substitution positions were found to differ between the upper and lower respiratory tract samples from all patients. However, the D222G/N substitution in hemagglutinin (HA) protein was the only amino acid substitution common to multiple patients. Furthermore, the substitution was detected only in the six samples from the lower respiratory tract. Therefore, it is important to investigate influenza A(H1N1)pdm09 virus populations using multiple paired samples from the upper and lower respiratory tract to avoid overlooking potentially important substitutions, especially in patients with severe disease. IMPORTANCE The D222G/N substitution in the hemagglutinin (HA) protein of influenza A(H1N1)pdm09 virus has been reported to be associated with disease severity and mortality in numerous previous studies. In the present study, 75% of lower respiratory samples contained heterogeneous influenza populations that carried different amino acids at position 222 of the HA protein, whereas all upper respiratory samples only contained the wild-type 222D. These results suggest the influenza A(H1N1)pdm09 virus has diversified inside the host owing to differences in tissue specificity. In this study, the within-host genetic diversity of influenza A(H1N1)pdm09 virus was investigated for the first time using next-generation sequencing analysis of the viral whole-genome in samples extracted from the upper and lower respiratory tracts of patients with severe disease.
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spelling pubmed-78455922021-01-29 Next-Generation Sequencing Analysis of the Within-Host Genetic Diversity of Influenza A(H1N1)pdm09 Viruses in the Upper and Lower Respiratory Tracts of Patients with Severe Influenza Takayama, Ikuyo Nguyen, Binh Gia Dao, Co Xuan Pham, Thach The Dang, Tuan Quoc Truong, Phuong Thai Do, Thanh Van Pham, Thuy Thi Phuong Fujisaki, Seiichiro Odagiri, Takato Hasegawa, Hideki Nakajima, Noriko mSphere Research Article The influenza A(H1N1)pdm09 virus emerged in April 2009 with an unusual incidence of severe disease and mortality, and currently circulates as a seasonal influenza virus. Previous studies using consensus viral genome sequencing data have overlooked the viral genomic and phenotypic diversity. Next-generation sequencing (NGS) may instead be used to characterize viral populations in an unbiased manner and to measure within-host genetic diversity. In this study, we used NGS analysis to investigate the within-host genetic diversity of influenza A(H1N1)pdm09 virus in the upper and lower respiratory samples from nine patients who were admitted to the intensive care unit (ICU). A total of 47 amino acid substitution positions were found to differ between the upper and lower respiratory tract samples from all patients. However, the D222G/N substitution in hemagglutinin (HA) protein was the only amino acid substitution common to multiple patients. Furthermore, the substitution was detected only in the six samples from the lower respiratory tract. Therefore, it is important to investigate influenza A(H1N1)pdm09 virus populations using multiple paired samples from the upper and lower respiratory tract to avoid overlooking potentially important substitutions, especially in patients with severe disease. IMPORTANCE The D222G/N substitution in the hemagglutinin (HA) protein of influenza A(H1N1)pdm09 virus has been reported to be associated with disease severity and mortality in numerous previous studies. In the present study, 75% of lower respiratory samples contained heterogeneous influenza populations that carried different amino acids at position 222 of the HA protein, whereas all upper respiratory samples only contained the wild-type 222D. These results suggest the influenza A(H1N1)pdm09 virus has diversified inside the host owing to differences in tissue specificity. In this study, the within-host genetic diversity of influenza A(H1N1)pdm09 virus was investigated for the first time using next-generation sequencing analysis of the viral whole-genome in samples extracted from the upper and lower respiratory tracts of patients with severe disease. American Society for Microbiology 2021-01-06 /pmc/articles/PMC7845592/ /pubmed/33408229 http://dx.doi.org/10.1128/mSphere.01043-20 Text en Copyright © 2021 Takayama et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Takayama, Ikuyo
Nguyen, Binh Gia
Dao, Co Xuan
Pham, Thach The
Dang, Tuan Quoc
Truong, Phuong Thai
Do, Thanh Van
Pham, Thuy Thi Phuong
Fujisaki, Seiichiro
Odagiri, Takato
Hasegawa, Hideki
Nakajima, Noriko
Next-Generation Sequencing Analysis of the Within-Host Genetic Diversity of Influenza A(H1N1)pdm09 Viruses in the Upper and Lower Respiratory Tracts of Patients with Severe Influenza
title Next-Generation Sequencing Analysis of the Within-Host Genetic Diversity of Influenza A(H1N1)pdm09 Viruses in the Upper and Lower Respiratory Tracts of Patients with Severe Influenza
title_full Next-Generation Sequencing Analysis of the Within-Host Genetic Diversity of Influenza A(H1N1)pdm09 Viruses in the Upper and Lower Respiratory Tracts of Patients with Severe Influenza
title_fullStr Next-Generation Sequencing Analysis of the Within-Host Genetic Diversity of Influenza A(H1N1)pdm09 Viruses in the Upper and Lower Respiratory Tracts of Patients with Severe Influenza
title_full_unstemmed Next-Generation Sequencing Analysis of the Within-Host Genetic Diversity of Influenza A(H1N1)pdm09 Viruses in the Upper and Lower Respiratory Tracts of Patients with Severe Influenza
title_short Next-Generation Sequencing Analysis of the Within-Host Genetic Diversity of Influenza A(H1N1)pdm09 Viruses in the Upper and Lower Respiratory Tracts of Patients with Severe Influenza
title_sort next-generation sequencing analysis of the within-host genetic diversity of influenza a(h1n1)pdm09 viruses in the upper and lower respiratory tracts of patients with severe influenza
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845592/
https://www.ncbi.nlm.nih.gov/pubmed/33408229
http://dx.doi.org/10.1128/mSphere.01043-20
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