SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NFκB-dependent promoter antagonism in chicken cells.

James, J; Smith, N; Ross, C; Iqbal, M; Goodbourn, S; Digard, P; Barclay, WS; Shelton, H (2019) The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NFκB-dependent promoter antagonism in chicken cells. J Gen Virol, 100 (3). pp. 414-430. ISSN 1465-2099 https://doi.org/10.1099/jgv.0.001220
SGUL Authors: Goodbourn, Stephen Edward

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (5MB) | Preview
[img]
Preview
PDF Accepted Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

Abstract

The accessory protein, PB1-F2, of influenza A virus (IAV) functions in a chicken host to prolong infectious virus shedding and thus the transmission window. Here we show that this delay in virus clearance by PB1-F2 in chickens is accompanied by reduced transcript levels of type 1 interferon (IFN)-induced genes and NFκB-activated pro-inflammation cytokines. In vitro, two avian influenza isolate-derived PB1-F2 proteins, H9N2 UDL01 and H5N1 5092, exhibited the same antagonism of the IFN and pro-inflammation induction pathways seen in vivo, but to different extents. The two PB1-F2 proteins had different cellular localization in chicken cells, with H5N1 5092 being predominantly mitochondrial-associated and H9N2 UDL being cytoplasmic but not mitochondrial-localized. We hypothesized that PB1-F2 localization might influence the functionality of the protein during infection and that the protein sequence could alter cellular localization. We demonstrated that the sequence of the C-terminus of PB1-F2 determined cytoplasmic localization in chicken cells and this was linked with protein instability. Mitochondrial localization of PB1-F2 resulted in reduced antagonism of an NFκB-dependent promoter. In parallel, mitochondrial localization of PB1-F2 increased the potency of chicken IFN 2 induction antagonism. We suggest that mitochondrial localization of PB1-F2 restricts interaction with cytoplasmic-located IKKβ, reducing NFκB-responsive promoter antagonism, but enhances antagonism of the IFN2 promoter through interaction with the mitochondrial adaptor MAVS. Our study highlights the differential mechanisms by which IAV PB1-F2 protein can dampen the avian host innate signalling response.

Item Type: Article
Additional Information: © 2019 The Authors This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: 06 Biological Sciences, 07 Agricultural And Veterinary Sciences, 11 Medical And Health Sciences, Virology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: J Gen Virol
ISSN: 1465-2099
Language: eng
Dates:
DateEvent
1 March 2019Published
23 January 2019Published Online
25 December 2018Accepted
Publisher License: Creative Commons: Attribution 3.0
Projects:
Project IDFunderFunder ID
BB/K002465/1Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BBS/E/00001759Pirbright Institutehttp://dx.doi.org/10.13039/501100000870
BBS/E/I/00001650Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BBS/E/I/00007034Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BBS/E/I/00007038Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
PubMed ID: 30672726
Go to PubMed abstract
URI: http://sgultest.da.ulcc.ac.uk/id/eprint/110533
Publisher's version: https://doi.org/10.1099/jgv.0.001220

Actions (login required)

Edit Item Edit Item