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{Artarini:2019:10.1016/j.antiviral.2019.06.003,
author = {Artarini, A and Meyer, M and Shin, YJ and Huber, K and Hilz, N and Bracher, F and Eros, D and Orfi, L and Keri, G and Goedert, S and Neuenschwander, M and von, Kries J and Domovich-Eisenberg, Y and Dekel, N and Szabadkai, I and Lebendiker, M and Horváth, Z and Danieli, T and Livnah, O and Moncorgé, O and Frise, R and Barclay, W and Meyer, TF and Karlas, A},
doi = {10.1016/j.antiviral.2019.06.003},
journal = {Antiviral Research},
pages = {187--196},
title = {Regulation of influenza a virus mRNA splicing by CLK1},
url = {http://dx.doi.org/10.1016/j.antiviral.2019.06.003},
volume = {168},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Influenza A virus carries eight negative single-stranded RNAs and uses spliced mRNAs to increase the number of proteins produced from them. Several genome-wide screens for essential host factors for influenza A virus replication revealed a necessity for splicing and splicing-related factors, including Cdc-like kinase 1 (CLK1). This CLK family kinase plays a role in alternative splicing regulation through phosphorylation of serine-arginine rich (SR) proteins. To examine the influence that modulation of splicing regulation has on influenza infection, we analyzed the effect of CLK1 knockdown and inhibition. CLK1 knockdown in A549cells reduced influenza A/WSN/33 virus replication and increased the level of splicing of segment 7, encoding the viral M1 and M2 proteins. CLK1-/- mice infected with influenza A/England/195/2009 (H1N1pdm09) virus supported lower levels of virus replication than wild-type mice. Screening of newly developed CLK inhibitors revealed several compounds that have an effect on the level of splicing of influenza A gene segment M in different models and decrease influenza A/WSN/33 virus replication in A549cells. The promising inhibitor KH-CB19, an indole-based enaminonitrile with unique binding mode for CLK1, and its even more selective analogue NIH39 showed high specificity towards CLK1 and had a similar effect on influenza mRNA splicing regulation. Taken together, our findings indicate that targeting host factors that regulate splicing of influenza mRNAs may represent a novel therapeutic approach.
AU  - Artarini,A
AU  - Meyer,M
AU  - Shin,YJ
AU  - Huber,K
AU  - Hilz,N
AU  - Bracher,F
AU  - Eros,D
AU  - Orfi,L
AU  - Keri,G
AU  - Goedert,S
AU  - Neuenschwander,M
AU  - von,Kries J
AU  - Domovich-Eisenberg,Y
AU  - Dekel,N
AU  - Szabadkai,I
AU  - Lebendiker,M
AU  - Horváth,Z
AU  - Danieli,T
AU  - Livnah,O
AU  - Moncorgé,O
AU  - Frise,R
AU  - Barclay,W
AU  - Meyer,TF
AU  - Karlas,A
DO  - 10.1016/j.antiviral.2019.06.003
EP  - 196
PY  - 2019///
SN  - 0166-3542
SP  - 187
TI  - Regulation of influenza a virus mRNA splicing by CLK1
T2  - Antiviral Research
UR  - http://dx.doi.org/10.1016/j.antiviral.2019.06.003
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31176694
UR  - http://hdl.handle.net/10044/1/70957
VL  - 168
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