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

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Abstract

Continued circulation of A/H5N1 influenzaviruses of the A/goose/Guangdong/1/96 lineage in poultry has resulted in the diversificationin 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 influenzaA 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.

Original languageEnglish
Article numbere0020023
Pages (from-to)e0020023
JournalmSphere
Volume8
Issue number4
Early online date10 Jul 2023
DOIs
Publication statusPublished - 24 Aug 2023

Bibliographical note

Funding Information:
This work was through NIAID-NIH contract HHSN272201400008C, H2020 program COMPARE (643476), NWO VIDI grant (91715372), and the 2018 Stevin award.

Publisher Copyright:
© 2023 Herfst et al.

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