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Outbreak severity of highly pathogenic avian influenza A(H5N8) viruses is inversely correlated to polymerase complex activity and interferon induction

Vigeveno, R M; Poen, M J; Parker, E; Holwerda, M; de Haan, K; van Montfort, T; Lewis, N S; Russell, C A; Fouchier, R AM; de Jong, M D; Eggink, D

Authors

R M Vigeveno

M J Poen

E Parker

M Holwerda

K de Haan

T van Montfort

N S Lewis

C A Russell

R AM Fouchier

M D de Jong

D Eggink



Abstract

Highly pathogenic avian influenza A(H5N8) viruses first emerged in China in 2010 and in 2014 spread throughout Asia and to Europe and The United States via migrating birds. Influenza A(H5N8) viruses were first detected in the Netherlands in 2014 and caused five outbreaks in poultry farms, but were infrequently detected in wild birds. In 2016, influenza A(H5N8) viruses were reintroduced into the Netherlands resulting in eight poultry farms outbreaks. This outbreak resulted in numerous dead wild birds with severe pathology. Phylogenetic analysis showed that the polymerase genes of these viruses had undergone extensive reassortment between outbreaks. Here, we investigated the differences in virulence between the 2014-15 and 2016-17 outbreak by characterizing the polymerase complex of influenza A(H5N8) viruses from both outbreaks. We found that viruses from the 2014-15 outbreak had significantly higher polymerase complex activity in both human and avian cell lines. No apparent differences in the balance between transcription and replication of the viral genome were observed. Interestingly, the 2014-15 polymerase complexes induced significantly higher amounts of IFNβ compared to the polymerase complexes of 2016-17 viruses, mediated via RIG-I. Inoculation of primary duck cells with recombinant influenza A(H5N8) viruses, including viruses with reassorted polymerase complexes, showed that the polymerase complexes from the 2014-15 outbreak induced higher levels of IFNβ despite relatively minor differences in replication capacity. Together, these data suggest that despite the lower levels of polymerase activity, the higher 2016-17 influenza A(H5N8) virulence may be attributed to the lower level of activation of the innate immune system.

Citation

Vigeveno, R. M., Poen, M. J., Parker, E., Holwerda, M., de Haan, K., van Montfort, T., …Eggink, D. (2020). Outbreak severity of highly pathogenic avian influenza A(H5N8) viruses is inversely correlated to polymerase complex activity and interferon induction. Journal of Virology, https://doi.org/10.1128/JVI.00375-20

Journal Article Type Article
Acceptance Date Mar 1, 2020
Publication Date Apr 1, 2020
Deposit Date Apr 23, 2020
Journal Journal of Virology
Print ISSN 0022-538X
Electronic ISSN 1098-5514
Publisher American Society for Microbiology
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1128/JVI.00375-20
Public URL https://rvc-repository.worktribe.com/output/1377834


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