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. GoldhillAartjan J. W. te VelthuisRobert A. FletcherPinky LangatMaria ZambonAngie 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{Goldhill:2018:10.1073/pnas.1811345115,
author = {Goldhill, DH and te, Velthuis AJW and Fletcher, RA and Langat, P and Zambon, M and Lackenby, A and Barclay, WS},
doi = {10.1073/pnas.1811345115},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
pages = {11613--11618},
title = {The mechanism of resistance to favipiravir in influenza},
url = {http://dx.doi.org/10.1073/pnas.1811345115},
volume = {115},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Favipiravir is a broad-spectrum antiviral that has shown promise in treatment of influenza virus infections. While emergence of resistance has been observed for many antiinfluenza drugs, to date, clinical trials and laboratory studies of favipiravir have not yielded resistant viruses. Here we show evolution of resistance to favipiravir in the pandemic H1N1 influenza A virus in a laboratory setting. We found that two mutations were required for robust resistance to favipiravir. We demonstrate that a K229R mutation in motif F of the PB1 subunit of the influenza virus RNA-dependent RNA polymerase (RdRP) confers resistance to favipiravir in vitro and in cell culture. This mutation has a cost to viral fitness, but fitness can be restored by a P653L mutation in the PA subunit of the polymerase. K229R also conferred favipiravir resistance to RNA polymerases of other influenza A virus strains, and its location within a highly conserved structural feature of the RdRP suggests that other RNA viruses might also acquire resistance through mutations in motif F. The mutations identified here could be used to screen influenza virus-infected patients treated with favipiravir for the emergence of resistance.
AU - Goldhill,DH
AU - te,Velthuis AJW
AU - Fletcher,RA
AU - Langat,P
AU - Zambon,M
AU - Lackenby,A
AU - Barclay,WS
DO - 10.1073/pnas.1811345115
EP - 11618
PY - 2018///
SN - 0027-8424
SP - 11613
TI - The mechanism of resistance to favipiravir in influenza
T2 - Proceedings of the National Academy of Sciences of the United States of America
UR - http://dx.doi.org/10.1073/pnas.1811345115
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000449459000079&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://www.pnas.org/content/115/45/11613/
UR - http://hdl.handle.net/10044/1/65134
VL - 115
ER -