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Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection

The continuing pandemic threat posed by avian influenza A/H5N1 viruses calls for improved insights into their evolution during human infection. We performed whole genome deep sequencing of respiratory specimens from 44 H5N1-infected individuals from Indonesia and found substantial within-host viral...

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Autores principales: Welkers, Matthijs R.A., Pawestri, Hana A., Fonville, Judy M., Sampurno, Ondri D., Pater, Maarten, Holwerda, Melle, Han, Alvin X., Russell, Colin A., Jeeninga, Rienk E., Setiawaty, Vivi, de Jong, Menno D., Eggink, Dirk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455201/
https://www.ncbi.nlm.nih.gov/pubmed/30866780
http://dx.doi.org/10.1080/22221751.2019.1575700
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author Welkers, Matthijs R.A.
Pawestri, Hana A.
Fonville, Judy M.
Sampurno, Ondri D.
Pater, Maarten
Holwerda, Melle
Han, Alvin X.
Russell, Colin A.
Jeeninga, Rienk E.
Setiawaty, Vivi
de Jong, Menno D.
Eggink, Dirk
author_facet Welkers, Matthijs R.A.
Pawestri, Hana A.
Fonville, Judy M.
Sampurno, Ondri D.
Pater, Maarten
Holwerda, Melle
Han, Alvin X.
Russell, Colin A.
Jeeninga, Rienk E.
Setiawaty, Vivi
de Jong, Menno D.
Eggink, Dirk
author_sort Welkers, Matthijs R.A.
collection PubMed
description The continuing pandemic threat posed by avian influenza A/H5N1 viruses calls for improved insights into their evolution during human infection. We performed whole genome deep sequencing of respiratory specimens from 44 H5N1-infected individuals from Indonesia and found substantial within-host viral diversity. At nearly 30% of genome positions multiple amino acids were observed within or across samples, including positions implicated in aerosol transmission between ferrets. Amino acid variants detected our cohort were often found more frequently in available H5N1 sequences of human than avian isolates. We additionally identified previously unreported amino acid variants and multiple variants that increased in proportion over time in available sequential samples. Given the importance of the polymerase complex for host adaptation, we tested 121 amino acid variants found in the PB2, PB1 and PA subunits for their effects on polymerase activity in human cells. We identified multiple single amino acid variants in all three polymerase subunits that substantially increase polymerase activity including some with effects comparable to that of the widely recognized adaption and virulence marker PB2-E627 K. These results indicate highly dynamic evolutionary processes during human H5N1 virus infection and the potential existence of previously undocumented adaptive pathways.
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spelling pubmed-64552012019-04-18 Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection Welkers, Matthijs R.A. Pawestri, Hana A. Fonville, Judy M. Sampurno, Ondri D. Pater, Maarten Holwerda, Melle Han, Alvin X. Russell, Colin A. Jeeninga, Rienk E. Setiawaty, Vivi de Jong, Menno D. Eggink, Dirk Emerg Microbes Infect Article The continuing pandemic threat posed by avian influenza A/H5N1 viruses calls for improved insights into their evolution during human infection. We performed whole genome deep sequencing of respiratory specimens from 44 H5N1-infected individuals from Indonesia and found substantial within-host viral diversity. At nearly 30% of genome positions multiple amino acids were observed within or across samples, including positions implicated in aerosol transmission between ferrets. Amino acid variants detected our cohort were often found more frequently in available H5N1 sequences of human than avian isolates. We additionally identified previously unreported amino acid variants and multiple variants that increased in proportion over time in available sequential samples. Given the importance of the polymerase complex for host adaptation, we tested 121 amino acid variants found in the PB2, PB1 and PA subunits for their effects on polymerase activity in human cells. We identified multiple single amino acid variants in all three polymerase subunits that substantially increase polymerase activity including some with effects comparable to that of the widely recognized adaption and virulence marker PB2-E627 K. These results indicate highly dynamic evolutionary processes during human H5N1 virus infection and the potential existence of previously undocumented adaptive pathways. Taylor & Francis 2019-02-17 /pmc/articles/PMC6455201/ /pubmed/30866780 http://dx.doi.org/10.1080/22221751.2019.1575700 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Welkers, Matthijs R.A.
Pawestri, Hana A.
Fonville, Judy M.
Sampurno, Ondri D.
Pater, Maarten
Holwerda, Melle
Han, Alvin X.
Russell, Colin A.
Jeeninga, Rienk E.
Setiawaty, Vivi
de Jong, Menno D.
Eggink, Dirk
Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection
title Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection
title_full Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection
title_fullStr Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection
title_full_unstemmed Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection
title_short Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection
title_sort genetic diversity and host adaptation of avian h5n1 influenza viruses during human infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455201/
https://www.ncbi.nlm.nih.gov/pubmed/30866780
http://dx.doi.org/10.1080/22221751.2019.1575700
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