Notable Recent Publications

These are some recent publications which give a flavour of the research from the Barclay lab. For a complete list of publications, please see below.

Species difference in ANP32A underlies influenza A virus polymerase host restriction. Nature (2016).
Jason S. Long, Efstathios S. Giotis, Olivier Moncorgé, Rebecca Frise, Bhakti Mistry, Joe James, Mireille Morisson, Munir Iqbal, Alain Vignal, Michael A. Skinner & Wendy S. Barclay

This paper identified a key factor that explained why the polymerases from avian influenza viruses are restricted in humans.  For more, please see the associated New and Views.

See our latest ANP32 papers here: eLIFE, Journal of Virology, Journal of Virology.

The mechanism of resistance to favipiravir in influenza. PNAS (2018).
Daniel H. Goldhill, Aartjan J. W. te Velthuis, Robert A. Fletcher, Pinky Langat, Maria Zambon, Angie Lackenby & Wendy S. Barclay

This paper showed how influenza could evolve resistance to favipiravir, an antiviral that may be used to treat influenza. The residue that mutated to give resistance was highly conserved suggesting that the mechanism of resistance may be applicable to other RNA viruses.

Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice. Plos Path. (2018).
Hui Li*, Konrad C. Bradley*, Jason S. Long, Rebecca Frise, Jonathan W. Ashcroft, Lorian C. Hartgroves, Holly Shelton, Spyridon Makris, Cecilia Johansson, Bin Cao & Wendy S. Barclay

Why do avian influenza viruses like H5N1 cause such severe disease in humans? This paper demonstrated that H5N1 viruses replicate better than human viruses in myeloid cells from mice leading to a cytokine storm and more severe disease.

Citation

BibTex format

@article{James:2019:10.1099/jgv.0.001220,
author = {James, J and Smith, N and Ross, C and Iqbal, M and Goodbourn, S and Digard, P and Barclay, WS and Shelton, H},
doi = {10.1099/jgv.0.001220},
journal = {J Gen Virol},
pages = {414--430},
title = {The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NFκB-dependent promoter antagonism in chicken cells.},
url = {http://dx.doi.org/10.1099/jgv.0.001220},
volume = {100},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - James,J
AU  - Smith,N
AU  - Ross,C
AU  - Iqbal,M
AU  - Goodbourn,S
AU  - Digard,P
AU  - Barclay,WS
AU  - Shelton,H
DO  - 10.1099/jgv.0.001220
EP  - 430
PY  - 2019///
SP  - 414
TI  - The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NFκB-dependent promoter antagonism in chicken cells.
T2  - J Gen Virol
UR  - http://dx.doi.org/10.1099/jgv.0.001220
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30672726
VL  - 100
ER  -
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Contact us

For any enquiries related to this group, please contact:

Professor Wendy Barclay
Chair in Influenza Virology 
+44 (020) 7594 5035
w.barclay@imperial.ac.uk