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{Li:2018:10.1371/journal.ppat.1006821,
author = {Li, H and Bradley, KC and Long, JS and Frise, R and Ashcroft, JW and Hartgroves, LC and Shelton, H and Makris, S and Johansson, C and Cao, B and Barclay, WS},
doi = {10.1371/journal.ppat.1006821},
journal = {PLoS Pathogens},
title = {Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice.},
url = {http://dx.doi.org/10.1371/journal.ppat.1006821},
volume = {14},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The highly pathogenic avian influenza (HPAI) H5N1 influenza virus has been a public health concern for more than a decade because of its frequent zoonoses and the high case fatality rate associated with human infections. Severe disease following H5N1 influenza infection is often associated with dysregulated host innate immune response also known as cytokine storm but the virological and cellular basis of these responses has not been clearly described. We rescued a series of 6:2 reassortant viruses that combined a PR8 HA/NA pairing with the internal gene segments from human adapted H1N1, H3N2, or avian H5N1 viruses and found that mice infected with the virus with H5N1 internal genes suffered severe weight loss associated with increased lung cytokines but not high viral load. This phenotype did not map to the NS gene segment, and NS1 protein of H5N1 virus functioned as a type I IFN antagonist as efficient as NS1 of H1N1 or H3N2 viruses. Instead we discovered that the internal genes of H5N1 virus supported a much higher level of replication of viral RNAs in myeloid cells in vitro but not in epithelial cells and that this was associated with high induction of type I IFN in myeloid cells. We also found that in vivo during H5N1 recombinant virus infection cells of haematopoetic origin were infected and produced type I IFN and proinflammatory cytokines. Taken together our data infer that human and avian influenza viruses are differently controlled by host factors in alternative cell types; internal gene segments of avian H5N1 virus uniquely drove high viral replication in myeloid cells, which triggered an excessive cytokine production, resulting in severe immunopathology.
AU  - Li,H
AU  - Bradley,KC
AU  - Long,JS
AU  - Frise,R
AU  - Ashcroft,JW
AU  - Hartgroves,LC
AU  - Shelton,H
AU  - Makris,S
AU  - Johansson,C
AU  - Cao,B
AU  - Barclay,WS
DO  - 10.1371/journal.ppat.1006821
PY  - 2018///
SN  - 1553-7366
TI  - Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice.
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1006821
UR  - http://hdl.handle.net/10044/1/55858
VL  - 14
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