In this section
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).
, , , , ,
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.
@article{Singanayagam:2019:10.1128/JVI.00058-19,
author = {Singanayagam, A and Zambon, M and Barclay, W},
doi = {10.1128/JVI.00058-19},
journal = {Journal of Virology},
title = {Influenza virus with increased pH of HA activation has improved replication in cell culture but at the cost of infectivity in human airway epithelium.},
url = {http://dx.doi.org/10.1128/JVI.00058-19},
volume = {98},
year = {2019}
}
TY - JOUR
AB - Pandemic H1N1 (pH1N1) influenza virus emerged from swine in 2009 with adequate capability to infect and transmit between people. In subsequent years it has circulated as a seasonal virus and evolved further human-adapting mutations. Mutations in the haemagglutinin (HA) stalk that increase pH stability have been associated with human adaptation and airborne transmission of pH1N1 virus. Yet, our understanding of how pH stability impacts virus/host interactions is incomplete. Here, using recombinant viruses with point mutations that alter the pH stability of pH1N1 HA, we found distinct effects on virus phenotypes in different experimental models. Increased pH sensitivity enabled virus to uncoat in endosomes more efficiently, manifesting as increased replication rate in typical continuous cell cultures under single-cycle conditions. A more acid labile HA also conferred a small reduction in sensitivity to antiviral therapeutics that act at the pH-sensitive HA fusion step. Conversely, in primary human airway epithelium cultured at air-liquid interface, increased pH sensitivity attenuated multicycle viral replication, by compromising virus survival in the extracellular microenvironment. In a mouse model of influenza pathogenicity, there was an optimum HA activation pH and viruses with either more or less pH stable HA were less virulent. Opposing pressures inside and outside the host cell that determine pH stability may influence zoonotic potential. The distinct effects that changes in pH stability exert on viral phenotypes underscore the importance of using the most appropriate systems for assessing virus titre and fitness, which has implications for vaccine manufacture, antiviral drug development and pandemic risk assessment.ImportanceThe pH stability of the haemagglutinin surface protein varies between different influenza strains and subtypes and can affect the virus' ability to replicate and transmit. Here, we demonstrate a delicate balance the virus strikes within and
AU - Singanayagam,A
AU - Zambon,M
AU - Barclay,W
DO - 10.1128/JVI.00058-19
PY - 2019///
SN - 0022-538X
TI - Influenza virus with increased pH of HA activation has improved replication in cell culture but at the cost of infectivity in human airway epithelium.
T2 - Journal of Virology
UR - http://dx.doi.org/10.1128/JVI.00058-19
UR - https://www.ncbi.nlm.nih.gov/pubmed/31189708
UR - http://hdl.handle.net/10044/1/73171
VL - 98
ER -
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