Cargando…
A Dutch highly pathogenic H5N6 avian influenza virus showed remarkable tropism for extra-respiratory organs and caused severe disease but was not transmissible via air in the ferret model
Continued circulation of A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage in poultry has resulted in the diversification in multiple genetic and antigenic clades. Since 2009, clade 2.3.4.4 hemagglutinin (HA) containing viruses harboring the internal and neuraminidase (NA) genes of othe...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449504/ https://www.ncbi.nlm.nih.gov/pubmed/37428085 http://dx.doi.org/10.1128/msphere.00200-23 |
_version_ | 1785094966306930688 |
---|---|
author | Herfst, Sander Begeman, Lineke Spronken, Monique I. Poen, Marjolein J. Eggink, Dirk de Meulder, Dennis Lexmond, Pascal Bestebroer, Theo M. Koopmans, Marion P. G. Kuiken, Thijs Richard, Mathilde Fouchier, Ron A. M. |
author_facet | Herfst, Sander Begeman, Lineke Spronken, Monique I. Poen, Marjolein J. Eggink, Dirk de Meulder, Dennis Lexmond, Pascal Bestebroer, Theo M. Koopmans, Marion P. G. Kuiken, Thijs Richard, Mathilde Fouchier, Ron A. M. |
author_sort | Herfst, Sander |
collection | PubMed |
description | Continued circulation of A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage in poultry has resulted in the diversification in multiple genetic and antigenic clades. Since 2009, clade 2.3.4.4 hemagglutinin (HA) containing viruses harboring the internal and neuraminidase (NA) genes of other avian influenza A viruses have been detected. As a result, various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8 have been identified. As of January 2023, 83 humans have been infected with A/H5N6 viruses, thereby posing an apparent risk for public health. Here, as part of a risk assessment, the in vitro and in vivo characterization of A/H5N6 A/black-headed gull/Netherlands/29/2017 is described. This A/H5N6 virus was not transmitted between ferrets via the air but was of unexpectedly high pathogenicity compared to other described A/H5N6 viruses. The virus replicated and caused severe lesions not only in respiratory tissues but also in multiple extra-respiratory tissues, including brain, liver, pancreas, spleen, lymph nodes, and adrenal gland. Sequence analyses demonstrated that the well-known mammalian adaptation substitution D701N was positively selected in almost all ferrets. In the in vitro experiments, no other known viral phenotypic properties associated with mammalian adaptation or increased pathogenicity were identified. The lack of transmission via the air and the absence of mammalian adaptation markers suggest that the public health risk of this virus is low. The high pathogenicity of this virus in ferrets could not be explained by the known mammalian pathogenicity factors and should be further studied. IMPORTANCE: Avian influenza A/H5 viruses can cross the species barrier and infect humans. These infections can have a fatal outcome, but fortunately these influenza A/H5 viruses do not spread between humans. However, the extensive circulation and reassortment of A/H5N6 viruses in poultry and wild birds warrant risk assessments of circulating strains. Here an in-depth characterization of the properties of an avian A/H5N6 influenza virus isolated from a black-headed gull in the Netherlands was performed in vitro and in vivo, in ferrets. The virus was not transmissible via the air but caused severe disease and spread to extra-respiratory organs. Apart from the detection in ferrets of a mutation that increased virus replication, no other mammalian adaptation phenotypes were identified. Our results suggest that the risk of this avian A/H5N6 virus for public health is low. The underlying reasons for the high pathogenicity of this virus are unexplained and should be further studied. |
format | Online Article Text |
id | pubmed-10449504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-104495042023-08-25 A Dutch highly pathogenic H5N6 avian influenza virus showed remarkable tropism for extra-respiratory organs and caused severe disease but was not transmissible via air in the ferret model Herfst, Sander Begeman, Lineke Spronken, Monique I. Poen, Marjolein J. Eggink, Dirk de Meulder, Dennis Lexmond, Pascal Bestebroer, Theo M. Koopmans, Marion P. G. Kuiken, Thijs Richard, Mathilde Fouchier, Ron A. M. mSphere Research Article Continued circulation of A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage in poultry has resulted in the diversification in multiple genetic and antigenic clades. Since 2009, clade 2.3.4.4 hemagglutinin (HA) containing viruses harboring the internal and neuraminidase (NA) genes of other avian influenza A viruses have been detected. As a result, various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8 have been identified. As of January 2023, 83 humans have been infected with A/H5N6 viruses, thereby posing an apparent risk for public health. Here, as part of a risk assessment, the in vitro and in vivo characterization of A/H5N6 A/black-headed gull/Netherlands/29/2017 is described. This A/H5N6 virus was not transmitted between ferrets via the air but was of unexpectedly high pathogenicity compared to other described A/H5N6 viruses. The virus replicated and caused severe lesions not only in respiratory tissues but also in multiple extra-respiratory tissues, including brain, liver, pancreas, spleen, lymph nodes, and adrenal gland. Sequence analyses demonstrated that the well-known mammalian adaptation substitution D701N was positively selected in almost all ferrets. In the in vitro experiments, no other known viral phenotypic properties associated with mammalian adaptation or increased pathogenicity were identified. The lack of transmission via the air and the absence of mammalian adaptation markers suggest that the public health risk of this virus is low. The high pathogenicity of this virus in ferrets could not be explained by the known mammalian pathogenicity factors and should be further studied. IMPORTANCE: Avian influenza A/H5 viruses can cross the species barrier and infect humans. These infections can have a fatal outcome, but fortunately these influenza A/H5 viruses do not spread between humans. However, the extensive circulation and reassortment of A/H5N6 viruses in poultry and wild birds warrant risk assessments of circulating strains. Here an in-depth characterization of the properties of an avian A/H5N6 influenza virus isolated from a black-headed gull in the Netherlands was performed in vitro and in vivo, in ferrets. The virus was not transmissible via the air but caused severe disease and spread to extra-respiratory organs. Apart from the detection in ferrets of a mutation that increased virus replication, no other mammalian adaptation phenotypes were identified. Our results suggest that the risk of this avian A/H5N6 virus for public health is low. The underlying reasons for the high pathogenicity of this virus are unexplained and should be further studied. American Society for Microbiology 2023-07-10 /pmc/articles/PMC10449504/ /pubmed/37428085 http://dx.doi.org/10.1128/msphere.00200-23 Text en Copyright © 2023 Herfst 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 Herfst, Sander Begeman, Lineke Spronken, Monique I. Poen, Marjolein J. Eggink, Dirk de Meulder, Dennis Lexmond, Pascal Bestebroer, Theo M. Koopmans, Marion P. G. Kuiken, Thijs Richard, Mathilde Fouchier, Ron A. M. A Dutch highly pathogenic H5N6 avian influenza virus showed remarkable tropism for extra-respiratory organs and caused severe disease but was not transmissible via air in the ferret model |
title | A Dutch highly pathogenic H5N6 avian influenza virus showed remarkable tropism for extra-respiratory organs and caused severe disease but was not transmissible via air in the ferret model |
title_full | A Dutch highly pathogenic H5N6 avian influenza virus showed remarkable tropism for extra-respiratory organs and caused severe disease but was not transmissible via air in the ferret model |
title_fullStr | A Dutch highly pathogenic H5N6 avian influenza virus showed remarkable tropism for extra-respiratory organs and caused severe disease but was not transmissible via air in the ferret model |
title_full_unstemmed | A Dutch highly pathogenic H5N6 avian influenza virus showed remarkable tropism for extra-respiratory organs and caused severe disease but was not transmissible via air in the ferret model |
title_short | A Dutch highly pathogenic H5N6 avian influenza virus showed remarkable tropism for extra-respiratory organs and caused severe disease but was not transmissible via air in the ferret model |
title_sort | dutch highly pathogenic h5n6 avian influenza virus showed remarkable tropism for extra-respiratory organs and caused severe disease but was not transmissible via air in the ferret model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449504/ https://www.ncbi.nlm.nih.gov/pubmed/37428085 http://dx.doi.org/10.1128/msphere.00200-23 |
work_keys_str_mv | AT herfstsander adutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT begemanlineke adutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT spronkenmoniquei adutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT poenmarjoleinj adutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT egginkdirk adutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT demeulderdennis adutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT lexmondpascal adutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT bestebroertheom adutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT koopmansmarionpg adutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT kuikenthijs adutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT richardmathilde adutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT fouchierronam adutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT herfstsander dutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT begemanlineke dutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT spronkenmoniquei dutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT poenmarjoleinj dutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT egginkdirk dutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT demeulderdennis dutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT lexmondpascal dutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT bestebroertheom dutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT koopmansmarionpg dutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT kuikenthijs dutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT richardmathilde dutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel AT fouchierronam dutchhighlypathogenich5n6avianinfluenzavirusshowedremarkabletropismforextrarespiratoryorgansandcausedseverediseasebutwasnottransmissibleviaairintheferretmodel |