Research output: Contribution to journal › Article › Academic › peer-review
Outbreak Severity of Highly Pathogenic Avian Influenza A(H5N8) Viruses Is Inversely Correlated to Polymerase Complex Activity and Interferon Induction. / Vigeveno, René M.; Poen, Marjolein J.; Parker, Edyth et al.
In: Journal of virology, Vol. 94, No. 11, e00375-20, 01.06.2020.Research output: Contribution to journal › Article › Academic › peer-review
}
TY - JOUR
T1 - Outbreak Severity of Highly Pathogenic Avian Influenza A(H5N8) Viruses Is Inversely Correlated to Polymerase Complex Activity and Interferon Induction
AU - Vigeveno, René M.
AU - Poen, Marjolein J.
AU - Parker, Edyth
AU - Holwerda, Melle
AU - de Haan, Karen
AU - van Montfort, Thijs
AU - Lewis, Nicola S.
AU - Russell, Colin A.
AU - Fouchier, Ron A. M.
AU - de Jong, Menno D.
AU - Eggink, Dirk
N1 - Funding Information: This work was funded by a European Union H2020 Marie Curie International Incoming Fellowship to D.E., R.A.M.F. and N.S.L. are supported by NIAID/NIH contract HHSN272201400008C (CEIRS), and C.A.R. is supported by an ERC consolidator grant. E.P. is supported by the Gates Cambridge Trust (Bill and Melinda Gates Foundation; OPP1144). Publisher Copyright: Copyright © 2020 American Society for Microbiology. All Rights Reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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 farm 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 the 2016-17 outbreaks 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 than did those from the 2016-17 outbreak. 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 levels of interferon beta (IFN-β) than the polymerase complexes of the 2016-17 outbreak viruses, mediated via retinoic acid-inducible gene I (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 IFN-β 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) virus virulence may be attributed to the lower level of activation of the innate immune system.
AB - 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 farm 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 the 2016-17 outbreaks 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 than did those from the 2016-17 outbreak. 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 levels of interferon beta (IFN-β) than the polymerase complexes of the 2016-17 outbreak viruses, mediated via retinoic acid-inducible gene I (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 IFN-β 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) virus virulence may be attributed to the lower level of activation of the innate immune system.
KW - H5N8
KW - Influenza virus
KW - Interferon
KW - Polymerase complex
KW - Virology
KW - Virulence
UR - http://www.scopus.com/inward/record.url?scp=85084940324&partnerID=8YFLogxK
U2 - 10.1128/JVI.00375-20
DO - 10.1128/JVI.00375-20
M3 - Article
C2 - 32238581
VL - 94
JO - Journal of virology
JF - Journal of virology
SN - 0022-538X
IS - 11
M1 - e00375-20
ER -
ID: 11681917