Promotion of Hendra virus replication by microRNA 146a

Stewart, C. R., Marsh, G. A., Jenkins, K. A., Gantier, M. P., Tizard, M. L., Middleton, D., Lowenthal, J. W., Haining, J., Izzard, L., Gough, T. J., Deffrasnes, C., Stambas, J., Robinson, R., Heine, H. G., Pallister, J. A., Foord, A. J., Bean, A. G. and Wang, L. F. 2013, Promotion of Hendra virus replication by microRNA 146a, Journal of virology, vol. 87, no. 7, pp. 3782-3791.

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Title Promotion of Hendra virus replication by microRNA 146a
Author(s) Stewart, C. R.
Marsh, G. A.
Jenkins, K. A.
Gantier, M. P.
Tizard, M. L.
Middleton, D.
Lowenthal, J. W.
Haining, J.
Izzard, L.
Gough, T. J.
Deffrasnes, C.
Stambas, J.
Robinson, R.
Heine, H. G.
Pallister, J. A.
Foord, A. J.
Bean, A. G.
Wang, L. F.
Journal name Journal of virology
Volume number 87
Issue number 7
Start page 3782
End page 3791
Total pages 10
Publisher American Society for Microbiology
Place of publication Washington, D. C.
Publication date 2013-04
ISSN 0022-538X
1098-5514
Keyword(s) Hendra virus
host miRNA
Summary Hendra virus is a highly pathogenic zoonotic paramyxovirus in the genus Henipavirus. Thirty-nine outbreaks of Hendra virus have been reported since its initial identification in Queensland, Australia, resulting in seven human infections and four fatalities. Little is known about cellular host factors impacting Hendra virus replication. In this work, we demonstrate that Hendra virus makes use of a microRNA (miRNA) designated miR-146a, an NF-κB-responsive miRNA upregulated by several innate immune ligands, to favor its replication. miR-146a is elevated in the blood of ferrets and horses infected with Hendra virus and is upregulated by Hendra virus in human cells in vitro. Blocking miR-146a reduces Hendra virus replication in vitro, suggesting a role for this miRNA in Hendra virus replication. In silico analysis of miR-146a targets identified ring finger protein (RNF)11, a member of the A20 ubiquitin editing complex that negatively regulates NF-κB activity, as a novel component of Hendra virus replication. RNA interference-mediated silencing of RNF11 promotes Hendra virus replication in vitro, suggesting that increased NF-κB activity aids Hendra virus replication. Furthermore, overexpression of the IκB superrepressor inhibits Hendra virus replication. These studies are the first to demonstrate a host miRNA response to Hendra virus infection and suggest an important role for host miRNAs in Hendra virus disease.
Language eng
Field of Research 110804 - Medical Virology
Socio Economic Objective 920109 - Infectious Diseases
HERDC Research category C1 Refereed article in a scholarly journal
Persistent URL http://hdl.handle.net/10536/DRO/DU:30053439

Document type: Journal Article
Collection: School of Medicine
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Created: Thu, 04 Jul 2013, 13:40:03 EST by John Stambas

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