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
ABSTRACT 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) gene...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-08-01
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| Series: | mSphere |
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| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00200-23 |
| _version_ | 1827855274130538496 |
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| author | Sander Herfst Lineke Begeman Monique I. Spronken Marjolein J. Poen Dirk Eggink Dennis de Meulder Pascal Lexmond Theo M. Bestebroer Marion P. G. Koopmans Thijs Kuiken Mathilde Richard Ron A. M. Fouchier |
| author_facet | Sander Herfst Lineke Begeman Monique I. Spronken Marjolein J. Poen Dirk Eggink Dennis de Meulder Pascal Lexmond Theo M. Bestebroer Marion P. G. Koopmans Thijs Kuiken Mathilde Richard Ron A. M. Fouchier |
| author_sort | Sander Herfst |
| collection | DOAJ |
| description | ABSTRACT 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. |
| first_indexed | 2024-03-12T11:42:44Z |
| format | Article |
| id | doaj.art-9b22824140a048b8aa0c29f318100e50 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-03-12T11:42:44Z |
| publishDate | 2023-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-9b22824140a048b8aa0c29f318100e502023-08-31T14:26:41ZengAmerican Society for MicrobiologymSphere2379-50422023-08-018410.1128/msphere.00200-23A 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 modelSander Herfst0Lineke Begeman1Monique I. Spronken2Marjolein J. Poen3Dirk Eggink4Dennis de Meulder5Pascal Lexmond6Theo M. Bestebroer7Marion P. G. Koopmans8Thijs Kuiken9Mathilde Richard10Ron A. M. Fouchier11Department of Viroscience, Erasmus University Medical Center , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus University Medical Center , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus University Medical Center , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus University Medical Center , Rotterdam, the NetherlandsAcademic Medical Center Amsterdam, Laboratory of Experimental Virology , Amsterdam, the NetherlandsDepartment of Viroscience, Erasmus University Medical Center , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus University Medical Center , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus University Medical Center , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus University Medical Center , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus University Medical Center , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus University Medical Center , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus University Medical Center , Rotterdam, the NetherlandsABSTRACT 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.https://journals.asm.org/doi/10.1128/msphere.00200-23influenzaHPAIH5N6transmissionrisk assessmentferret |
| spellingShingle | Sander Herfst Lineke Begeman Monique I. Spronken Marjolein J. Poen Dirk Eggink Dennis de Meulder Pascal Lexmond Theo M. Bestebroer Marion P. G. Koopmans Thijs Kuiken Mathilde Richard Ron A. M. Fouchier 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 mSphere influenza HPAI H5N6 transmission risk assessment ferret |
| 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 | influenza HPAI H5N6 transmission risk assessment ferret |
| url | https://journals.asm.org/doi/10.1128/msphere.00200-23 |
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