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

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


    J Virol. 2020 Apr 1. pii: JVI.00375-20. doi: 10.1128/JVI.00375-20. [Epub ahead of print]
    Outbreak severity of highly pathogenic avian influenza A(H5N8) viruses is inversely correlated to polymerase complex activity and interferon induction.


    Vigeveno RM1, Poen MJ2, Parker E1, Holwerda M1, de Haan K1, van Montfort T1, Lewis NS3,4, Russell CA1, Fouchier RAM2, de Jong MD1, Eggink D5.

    Author information




    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.IMPORTANCE Compared to the 2014-15 outbreak, the 2016-17 outbreak of influenza A(H5N8) viruses in the Netherlands and Europe was more virulent; the number of dead or diseased wild birds found and the severity of pathological changes were higher during the 2016-17 outbreak. The polymerase complex plays an important role in influenza virus virulence and the gene segments of influenza A(H5N8) viruses reassorted extensively between the outbreaks. In this study the 2014-15 polymerase complexes were found to be more active, which is counterintuitive with the observed higher virulence of the 2016-17 viruses. Interestingly, the 2014-15 polymerase complexes also induced higher levels of IFNβ. These findings suggest that the higher virulence of influenza A(H5N8) viruses from the 2016-17 outbreak may be related to the lower induction of IFNβ. An attenuated interferon response could lead to increased dissemination increased dissemination, pathology and mortality as observed in (wild) birds infected during the 2016-17 outbreak.
    Copyright 2020 American Society for Microbiology.



    PMID:32238581DOI:10.1128/JVI.00375-20

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