Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets

ABSTRACT Since their emergence in 1997, A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage have diversified in multiple genetic and antigenic clades upon continued circulation in poultry in several countries in Eurasia and Africa. Since 2009, reassortant viruses carrying clade 2.3.4.4 he...

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Autores principales:	Sander Herfst, Chris K. P. Mok, Judith M. A. van den Brand, Stefan van der Vliet, Miruna E. Rosu, Monique I. Spronken, Zifeng Yang, Dennis de Meulder, Pascal Lexmond, Theo M. Bestebroer, J. S. Malik Peiris, Ron A. M. Fouchier, Mathilde Richard
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	2.3.4.4 ferrets highly pathogenic avian influenza pathogenesis transmission Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ff49b51255614091b9f13b7c1372c13f
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spelling	oai:doaj.org-article:ff49b51255614091b9f13b7c1372c13f2021-11-15T15:22:01ZHuman Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets10.1128/mSphere.00405-172379-5042https://doaj.org/article/ff49b51255614091b9f13b7c1372c13f2018-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00405-17https://doaj.org/toc/2379-5042ABSTRACT Since their emergence in 1997, A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage have diversified in multiple genetic and antigenic clades upon continued circulation in poultry in several countries in Eurasia and Africa. Since 2009, reassortant viruses carrying clade 2.3.4.4 hemagglutinin (HA) and internal and neuraminidase (NA) genes of influenza A viruses of different avian origin have been detected, yielding various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8. Previous studies reported on the low pathogenicity and lack of airborne transmission of A/H5N2 and A/H5N8 viruses in the ferret model. However, although A/H5N6 viruses are the only clade 2.3.4.4 viruses that crossed the species barrier and infected humans, the risk they pose for human health remains poorly characterized. Here, the characterization of A/H5N6 A/Guangzhou/39715/2014 virus in vitro and in ferrets is described. This A/H5N6 virus possessed high polymerase activity, mediated by the E627K substitution in the PB2 protein, which corresponds to only one biological trait out of the three that were previously shown to confer airborne transmissibility to A/H5N1 viruses between ferrets. This might explain its lack of airborne transmission between ferrets. After intranasal inoculation, A/H5N6 virus replicated to high titers in the respiratory tracts of ferrets and was excreted for at least 6 days. Moreover, A/H5N6 virus caused severe pneumonia in ferrets upon intratracheal inoculation. Thus, A/H5N6 virus causes a more severe disease in ferrets than previously investigated clade 2.3.4.4 viruses, but our results demonstrate that the risk from airborne spread is currently low. IMPORTANCE Avian influenza A viruses are a threat to human health, as they cross the species barrier and infect humans occasionally, often with severe outcome. The antigenic and genetic diversity of A/H5 viruses from the A/goose/Guangdong/1/96 lineage is increasing, due to continued circulation and reassortment in poultry, posing a constant risk for public health and requiring regular risk assessments. Here we performed an in-depth characterization of the properties of the newly emerged zoonotic A/H5N6 virus in vitro and in ferrets. The lack of airborne transmission in the ferret model indicates that A/H5N6 virus does not pose a direct public health threat, despite the fact that it can replicate to high titers throughout the respiratory tracts of ferrets and cause more severe disease than other clade 2.3.4.4 viruses.Sander HerfstChris K. P. MokJudith M. A. van den BrandStefan van der VlietMiruna E. RosuMonique I. SpronkenZifeng YangDennis de MeulderPascal LexmondTheo M. BestebroerJ. S. Malik PeirisRon A. M. FouchierMathilde RichardAmerican Society for Microbiologyarticle2.3.4.4ferretshighly pathogenic avian influenzapathogenesistransmissionMicrobiologyQR1-502ENmSphere, Vol 3, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	2.3.4.4 ferrets highly pathogenic avian influenza pathogenesis transmission Microbiology QR1-502
spellingShingle	2.3.4.4 ferrets highly pathogenic avian influenza pathogenesis transmission Microbiology QR1-502 Sander Herfst Chris K. P. Mok Judith M. A. van den Brand Stefan van der Vliet Miruna E. Rosu Monique I. Spronken Zifeng Yang Dennis de Meulder Pascal Lexmond Theo M. Bestebroer J. S. Malik Peiris Ron A. M. Fouchier Mathilde Richard Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets
description	ABSTRACT Since their emergence in 1997, A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage have diversified in multiple genetic and antigenic clades upon continued circulation in poultry in several countries in Eurasia and Africa. Since 2009, reassortant viruses carrying clade 2.3.4.4 hemagglutinin (HA) and internal and neuraminidase (NA) genes of influenza A viruses of different avian origin have been detected, yielding various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8. Previous studies reported on the low pathogenicity and lack of airborne transmission of A/H5N2 and A/H5N8 viruses in the ferret model. However, although A/H5N6 viruses are the only clade 2.3.4.4 viruses that crossed the species barrier and infected humans, the risk they pose for human health remains poorly characterized. Here, the characterization of A/H5N6 A/Guangzhou/39715/2014 virus in vitro and in ferrets is described. This A/H5N6 virus possessed high polymerase activity, mediated by the E627K substitution in the PB2 protein, which corresponds to only one biological trait out of the three that were previously shown to confer airborne transmissibility to A/H5N1 viruses between ferrets. This might explain its lack of airborne transmission between ferrets. After intranasal inoculation, A/H5N6 virus replicated to high titers in the respiratory tracts of ferrets and was excreted for at least 6 days. Moreover, A/H5N6 virus caused severe pneumonia in ferrets upon intratracheal inoculation. Thus, A/H5N6 virus causes a more severe disease in ferrets than previously investigated clade 2.3.4.4 viruses, but our results demonstrate that the risk from airborne spread is currently low. IMPORTANCE Avian influenza A viruses are a threat to human health, as they cross the species barrier and infect humans occasionally, often with severe outcome. The antigenic and genetic diversity of A/H5 viruses from the A/goose/Guangdong/1/96 lineage is increasing, due to continued circulation and reassortment in poultry, posing a constant risk for public health and requiring regular risk assessments. Here we performed an in-depth characterization of the properties of the newly emerged zoonotic A/H5N6 virus in vitro and in ferrets. The lack of airborne transmission in the ferret model indicates that A/H5N6 virus does not pose a direct public health threat, despite the fact that it can replicate to high titers throughout the respiratory tracts of ferrets and cause more severe disease than other clade 2.3.4.4 viruses.
format	article
author	Sander Herfst Chris K. P. Mok Judith M. A. van den Brand Stefan van der Vliet Miruna E. Rosu Monique I. Spronken Zifeng Yang Dennis de Meulder Pascal Lexmond Theo M. Bestebroer J. S. Malik Peiris Ron A. M. Fouchier Mathilde Richard
author_facet	Sander Herfst Chris K. P. Mok Judith M. A. van den Brand Stefan van der Vliet Miruna E. Rosu Monique I. Spronken Zifeng Yang Dennis de Meulder Pascal Lexmond Theo M. Bestebroer J. S. Malik Peiris Ron A. M. Fouchier Mathilde Richard
author_sort	Sander Herfst
title	Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets
title_short	Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets
title_full	Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets
title_fullStr	Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets
title_full_unstemmed	Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets
title_sort	human clade 2.3.4.4 a/h5n6 influenza virus lacks mammalian adaptation markers and does not transmit via the airborne route between ferrets
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/ff49b51255614091b9f13b7c1372c13f
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Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets

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