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

ABSTRACTThe 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-hos...
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Autor*in:	Matthijs R.A. Welkers [verfasserIn] Hana A. Pawestri [verfasserIn] Judy M. Fonville [verfasserIn] Ondri D. Sampurno [verfasserIn] Maarten Pater [verfasserIn] Melle Holwerda [verfasserIn] Alvin X. Han [verfasserIn] Colin A. Russell [verfasserIn] Rienk E. Jeeninga [verfasserIn] Vivi Setiawaty [verfasserIn] Menno D. de Jong [verfasserIn] Dirk Eggink [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Influenza H5N1 human adaptation polymerase complex

Übergeordnetes Werk:	In: Emerging Microbes and Infections - Taylor & Francis Group, 2013, 8(2019), 1, Seite 262-271
Übergeordnetes Werk:	volume:8 ; year:2019 ; number:1 ; pages:262-271

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1080/22221751.2019.1575700

Katalog-ID:	DOAJ091081394

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author_variant	m r w mrw h a p hap j m f jmf o d s ods m p mp m h mh a x h axh c a r car r e j rej v s vs m d d j mddj d e de
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allfields	10.1080/22221751.2019.1575700 doi (DE-627)DOAJ091081394 (DE-599)DOAJ712f439daf674623b0a0add46fe1fbc9 DE-627 ger DE-627 rakwb eng RC109-216 QR1-502 Matthijs R.A. Welkers verfasserin aut Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACTThe 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. Influenza H5N1 human adaptation polymerase complex Infectious and parasitic diseases Microbiology Hana A. Pawestri verfasserin aut Judy M. Fonville verfasserin aut Ondri D. Sampurno verfasserin aut Maarten Pater verfasserin aut Melle Holwerda verfasserin aut Alvin X. Han verfasserin aut Colin A. Russell verfasserin aut Rienk E. Jeeninga verfasserin aut Vivi Setiawaty verfasserin aut Menno D. de Jong verfasserin aut Dirk Eggink verfasserin aut In Emerging Microbes and Infections Taylor & Francis Group, 2013 8(2019), 1, Seite 262-271 (DE-627)726120715 (DE-600)2681359-2 22221751 nnns volume:8 year:2019 number:1 pages:262-271 https://doi.org/10.1080/22221751.2019.1575700 kostenfrei https://doaj.org/article/712f439daf674623b0a0add46fe1fbc9 kostenfrei https://www.tandfonline.com/doi/10.1080/22221751.2019.1575700 kostenfrei https://doaj.org/toc/2222-1751 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 1 262-271
spelling	10.1080/22221751.2019.1575700 doi (DE-627)DOAJ091081394 (DE-599)DOAJ712f439daf674623b0a0add46fe1fbc9 DE-627 ger DE-627 rakwb eng RC109-216 QR1-502 Matthijs R.A. Welkers verfasserin aut Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACTThe 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. Influenza H5N1 human adaptation polymerase complex Infectious and parasitic diseases Microbiology Hana A. Pawestri verfasserin aut Judy M. Fonville verfasserin aut Ondri D. Sampurno verfasserin aut Maarten Pater verfasserin aut Melle Holwerda verfasserin aut Alvin X. Han verfasserin aut Colin A. Russell verfasserin aut Rienk E. Jeeninga verfasserin aut Vivi Setiawaty verfasserin aut Menno D. de Jong verfasserin aut Dirk Eggink verfasserin aut In Emerging Microbes and Infections Taylor & Francis Group, 2013 8(2019), 1, Seite 262-271 (DE-627)726120715 (DE-600)2681359-2 22221751 nnns volume:8 year:2019 number:1 pages:262-271 https://doi.org/10.1080/22221751.2019.1575700 kostenfrei https://doaj.org/article/712f439daf674623b0a0add46fe1fbc9 kostenfrei https://www.tandfonline.com/doi/10.1080/22221751.2019.1575700 kostenfrei https://doaj.org/toc/2222-1751 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 1 262-271
allfields_unstemmed	10.1080/22221751.2019.1575700 doi (DE-627)DOAJ091081394 (DE-599)DOAJ712f439daf674623b0a0add46fe1fbc9 DE-627 ger DE-627 rakwb eng RC109-216 QR1-502 Matthijs R.A. Welkers verfasserin aut Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACTThe 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. Influenza H5N1 human adaptation polymerase complex Infectious and parasitic diseases Microbiology Hana A. Pawestri verfasserin aut Judy M. Fonville verfasserin aut Ondri D. Sampurno verfasserin aut Maarten Pater verfasserin aut Melle Holwerda verfasserin aut Alvin X. Han verfasserin aut Colin A. Russell verfasserin aut Rienk E. Jeeninga verfasserin aut Vivi Setiawaty verfasserin aut Menno D. de Jong verfasserin aut Dirk Eggink verfasserin aut In Emerging Microbes and Infections Taylor & Francis Group, 2013 8(2019), 1, Seite 262-271 (DE-627)726120715 (DE-600)2681359-2 22221751 nnns volume:8 year:2019 number:1 pages:262-271 https://doi.org/10.1080/22221751.2019.1575700 kostenfrei https://doaj.org/article/712f439daf674623b0a0add46fe1fbc9 kostenfrei https://www.tandfonline.com/doi/10.1080/22221751.2019.1575700 kostenfrei https://doaj.org/toc/2222-1751 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 1 262-271
allfieldsGer	10.1080/22221751.2019.1575700 doi (DE-627)DOAJ091081394 (DE-599)DOAJ712f439daf674623b0a0add46fe1fbc9 DE-627 ger DE-627 rakwb eng RC109-216 QR1-502 Matthijs R.A. Welkers verfasserin aut Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACTThe 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. Influenza H5N1 human adaptation polymerase complex Infectious and parasitic diseases Microbiology Hana A. Pawestri verfasserin aut Judy M. Fonville verfasserin aut Ondri D. Sampurno verfasserin aut Maarten Pater verfasserin aut Melle Holwerda verfasserin aut Alvin X. Han verfasserin aut Colin A. Russell verfasserin aut Rienk E. Jeeninga verfasserin aut Vivi Setiawaty verfasserin aut Menno D. de Jong verfasserin aut Dirk Eggink verfasserin aut In Emerging Microbes and Infections Taylor & Francis Group, 2013 8(2019), 1, Seite 262-271 (DE-627)726120715 (DE-600)2681359-2 22221751 nnns volume:8 year:2019 number:1 pages:262-271 https://doi.org/10.1080/22221751.2019.1575700 kostenfrei https://doaj.org/article/712f439daf674623b0a0add46fe1fbc9 kostenfrei https://www.tandfonline.com/doi/10.1080/22221751.2019.1575700 kostenfrei https://doaj.org/toc/2222-1751 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 1 262-271
allfieldsSound	10.1080/22221751.2019.1575700 doi (DE-627)DOAJ091081394 (DE-599)DOAJ712f439daf674623b0a0add46fe1fbc9 DE-627 ger DE-627 rakwb eng RC109-216 QR1-502 Matthijs R.A. Welkers verfasserin aut Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACTThe 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. Influenza H5N1 human adaptation polymerase complex Infectious and parasitic diseases Microbiology Hana A. Pawestri verfasserin aut Judy M. Fonville verfasserin aut Ondri D. Sampurno verfasserin aut Maarten Pater verfasserin aut Melle Holwerda verfasserin aut Alvin X. Han verfasserin aut Colin A. Russell verfasserin aut Rienk E. Jeeninga verfasserin aut Vivi Setiawaty verfasserin aut Menno D. de Jong verfasserin aut Dirk Eggink verfasserin aut In Emerging Microbes and Infections Taylor & Francis Group, 2013 8(2019), 1, Seite 262-271 (DE-627)726120715 (DE-600)2681359-2 22221751 nnns volume:8 year:2019 number:1 pages:262-271 https://doi.org/10.1080/22221751.2019.1575700 kostenfrei https://doaj.org/article/712f439daf674623b0a0add46fe1fbc9 kostenfrei https://www.tandfonline.com/doi/10.1080/22221751.2019.1575700 kostenfrei https://doaj.org/toc/2222-1751 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019 1 262-271
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authorswithroles_txt_mv	Matthijs R.A. Welkers @@aut@@ Hana A. Pawestri @@aut@@ Judy M. Fonville @@aut@@ Ondri D. Sampurno @@aut@@ Maarten Pater @@aut@@ Melle Holwerda @@aut@@ Alvin X. Han @@aut@@ Colin A. Russell @@aut@@ Rienk E. Jeeninga @@aut@@ Vivi Setiawaty @@aut@@ Menno D. de Jong @@aut@@ Dirk Eggink @@aut@@
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Welkers</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">ABSTRACTThe continuing pandemic threat posed by avian influenza A/H5N1 viruses calls for improved insights into their evolution during human infection. 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callnumber-first	R - Medicine
author	Matthijs R.A. Welkers
spellingShingle	Matthijs R.A. Welkers misc RC109-216 misc QR1-502 misc Influenza misc H5N1 misc human adaptation misc polymerase complex misc Infectious and parasitic diseases misc Microbiology Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection
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topic_title	RC109-216 QR1-502 Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection Influenza H5N1 human adaptation polymerase complex
topic	misc RC109-216 misc QR1-502 misc Influenza misc H5N1 misc human adaptation misc polymerase complex misc Infectious and parasitic diseases misc Microbiology
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title	Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection
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title_full	Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection
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author_browse	Matthijs R.A. Welkers Hana A. Pawestri Judy M. Fonville Ondri D. Sampurno Maarten Pater Melle Holwerda Alvin X. Han Colin A. Russell Rienk E. Jeeninga Vivi Setiawaty Menno D. de Jong Dirk Eggink
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title_sort	genetic diversity and host adaptation of avian h5n1 influenza viruses during human infection
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title_auth	Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection
abstract	ABSTRACTThe 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.
abstractGer	ABSTRACTThe 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.
abstract_unstemmed	ABSTRACTThe 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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title_short	Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection
url	https://doi.org/10.1080/22221751.2019.1575700 https://doaj.org/article/712f439daf674623b0a0add46fe1fbc9 https://www.tandfonline.com/doi/10.1080/22221751.2019.1575700 https://doaj.org/toc/2222-1751
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up_date	2024-07-03T18:19:44.989Z
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Genetic diversity and host adaptation of avian H5N1 influenza viruses during human infection

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