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.

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  • Journal article
    Everitt AR, Clare S, Pertel T, John SP, Wash RS, Smith SE, Chin CR, Feeley EM, Sims JS, Adams DJ, Wise HM, Kane L, Goulding D, Digard P, Anttila V, Baillie JK, Walsh TS, Hume DA, Palotie A, Xue Y, Colonna V, Tyler-Smith C, Dunning J, Gordon SB, GenISIS Investigators, MOSAIC Investigators, Smyth RL, Openshaw PJ, Dougan G, Brass AL, Kellam P, Everitt AR, Clare S, Pertel T, John SP, Wash RS, Smith SE, Chin CR, Feeley EM, Sims JS, Adams DJ, Wise HM, Kane L, Goulding D, Digard P, Anttila V, Baillie JK, Walsh TS, Hume DA, Palotie A, Xue Y, Colonna V, Tyler-Smith C, Dunning J, Gordon SB, The GenISIS Investigators, The MOSAIC Investigators, Smyth RL, Openshaw PJ, Dougan G, Brass AL, Kellam P, Everitt AR, Clare S, Pertel T, John SP, Wash RS, Smith SE, Chin CR, Feeley EM, Sims JS, Adams DJ, Wise HM, Kane L, Goulding D, Digard P, Anttila V, Baillie JK, Walsh TS, Hume DA, Palotie A, Xue Y, Colonna V, Tyler-Smith C, Dunning J, Gordon SB, Everingham K, Dawson H, Hope D, Ramsay P, Campbell A, Kerr S, Harrison D, Rowan K, Addison J, Donald N, Galt S, Noble D, Taylor J, Webster LL, Taylor Local LI, Aldridge LL, Dornan R, Richard C, Gilmour D, Simmons LL, White LL, Jardine C, Williams LL, Booth LL, Quasim T, Watson V, Henry P, Munro F, Bell L, Ruddy LL, Cole LL, Southward J, Allcoat P, Gray S, McDougall LL, Matheson J, Whiteside LL, Alcorn D, Rooney LL, Sundaram R, Imrie LL, Bruce J, McGuigan K, Moultrie LL, Cairns LL, Grant J, Hughes M, Murdoch LL, Davidson LL, Harris G, Paterson R, Wallis LL, Binning LL, Pollock M, Antonelli J, Duncan A, Gibson J, McCulloch C, Murphy L, Haley C, Faulkner G, Freeman T, Hume DA, Baillie JK, Chaussabel D, Adamson WE, Carman WF, Thompson C, Zambon MC, Aylin P, Ashby D, Barclay WS, Brett SJ, Cookson WO, Drumright LN, Dunning J, Elderfield RA, Garcia-Alvarez L, Gazzard BG, Griffiths MJ, Habibi MS, Hansel TT, Herberg JA, Holmes AH, Hussell T, Johnston SL, Kon OM, Levin M, Moffatt MF, Nadel S, Openshaw PJ, Warner JO, Aston SJ, Gordon SB, Hay A, McCauleet al., 2012,

    IFITM3 restricts the morbidity and mortality associated with influenza.

    , Nature, Vol: 484, Pages: 519-523

    The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses1, 2, 3, 4, 5, 6, 7. Both the magnitude and breadth of the IFITM proteins’ in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model8, we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 ‘Spanish’ influenza9, 10. Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and humans.

  • Journal article
    Lefevre EA, Carr BV, Inman CF, Prentice H, Brown IH, Brookes SM, Garcon F, Hill ML, Iqbal M, Elderfield RA, Barclay WS, Gubbins S, Bailey M, Charleston Bet al., 2012,

    Immune Responses in Pigs Vaccinated with Adjuvanted and Non-Adjuvanted A(H1N1)pdm/09 Influenza Vaccines Used in Human Immunization Programmes

    , PLOS One, Vol: 7, ISSN: 1932-6203

    Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus. Immunisation with the adjuvanted split vaccine induced significantly higher interferon gamma production, increased frequency of interferon gamma-producing cells and proliferation of CD4−CD8+ (cytotoxic) and CD4+CD8+ (helper) T cells, after in vitro re-stimulation. Despite significant differences in the magnitude and breadth of immune responses in the two vaccinated and mock treated groups, similar quantities of viral RNA were detected from the nasal cavity in all pigs after live virus challenge. The present study provides support for the use of the pig as a valid experimental model for influenza infections in humans, including the assessment of protective efficacy of therapeutic interventions.

  • Journal article
    Fouchier RAM, Garcia-Sastre A, Kawaoka Y, Barclay WS, Bouvier NM, Brown IH, Capua I, Chen H, Compans RW, Couch RB, Cox NJ, Doherty PC, Donis RO, Feldmann H, Guan Y, Katz J, Klenk HD, Kobinger G, Liu J, Liu X, Lowen A, Metten-Leiter TC, Osterhaus ADME, Palese P, Peiris JSM, Perez DR, Richt JA, Schultz-Cherry S, Steel J, Subbarao K, Swayne DE, Takimoto T, Tashiro M, Taubenberger JK, Thomas PG, Tripp RA, Tumpey TM, Webby RJ, Webster RGet al., 2012,

    Pause on Avian Flu Transmission Research

    , SCIENCE, Vol: 335, Pages: 400-401, ISSN: 0036-8075
  • Conference paper
    Sridhar S, Begom S, Bermingham A, Ziegler T, Roberts KL, Barclay WS, Openshaw P, Lalvani Aet al., 2012,

    Predominance of heterosubtypic IFN-gamma-only-secreting effector memory T cells in pandemic H1N1 naive adults

    , Pages: 2913-2924, ISSN: 1521-4141

    The 2009/10 pandemic (pH1N1) highlighted the need for vaccines conferring heterosubtypic immunity against antigenically shifted influenza strains. Although cross-reactive T cells are strong candidates for mediating heterosubtypic immunity, little is known about the population-level prevalence, frequency, and cytokine-secretion profile of heterosubtypic T cells to pH1N1. To assess this, pH1N1 sero-negative adults were recruited. Single-cell IFN-gamma and IL-2 cytokine-secretion profiles to internal proteins of pH1N1 or live virus were enumerated and characterised. Heterosubtypic T cells recognising pH1N1 core proteins were widely prevalent, being detected in 90% (30 of 33) of pH1N1-naive individuals. Although the last exposure to influenza was greater than 6 months ago, the frequency and proportion of the IFN-gamma-only-secreting T-cell subset was significantly higher than the IL-2-only-secreting subset. CD8(+) IFN-gamma-only-secreting heterosubtypic T cells were predominantly CCR7(-) CD45RA(-) effector-memory phenotype, expressing the tissue-homing receptor CXCR3 and degranulation marker CD107. Receipt of the 2008-09 influenza vaccine did not alter the frequency of these heterosubtypic T cells, highlighting the inability of current vaccines to maintain this heterosubtypic T-cell pool. The surprisingly high prevalence of pre-existing circulating pH1N1-specific CD8(+) IFN-gamma-only-secreting effector memory T cells with cytotoxic and lung-homing potential in pH1N1-seronegative adults may partly explain the low case fatality rate despite high rates of infection of the pandemic in young adults.

  • Journal article
    van Doremalen N, Shelton H, Roberts KL, Jones IM, Pickles RJ, Thompson CI, Barclay WSet al., 2011,

    A Single Amino Acid in the HA of pH1N1 2009 Influenza Virus Affects Cell Tropism in Human Airway Epithelium, but Not Transmission in Ferrets

    , PLOS ONE, Vol: 6, ISSN: 1932-6203
  • Journal article
    Roberts KL, Shelton H, Scull M, Pickles R, Barclay WSet al., 2011,

    Lack of transmission of a human influenza virus with avian receptor specificity between ferrets is not due to decreased virus shedding but rather a lower infectivity in vivo

    , JOURNAL OF GENERAL VIROLOGY, Vol: 92, Pages: 1822-1831, ISSN: 0022-1317
  • Journal article
    Foeglein A, Loucaides EM, Mura M, Wise HM, Barclay WS, Digard Pet al., 2011,

    Influence of PB2 host-range determinants on the intranuclear mobility of the influenza A virus polymerase

    , JOURNAL OF GENERAL VIROLOGY, Vol: 92, Pages: 1650-1661, ISSN: 0022-1317
  • Journal article
    Brookes DW, Miah S, Lackenby A, Hartgroves L, Barclay WSet al., 2011,

    Pandemic H1N1 2009 influenza virus with the H275Y oseltamivir resistance neuraminidase mutation shows a small compromise in enzyme activity and viral fitness

    , JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 66, Pages: 466-470, ISSN: 0305-7453
  • Journal article
    Loureiro S, Ren J, Phapugrangkul P, Colaco CA, Bailey CR, Shelton H, Molesti E, Temperton NJ, Barclay WS, Jones IMet al., 2011,

    Adjuvant-Free Immunization with Hemagglutinin-Fc Fusion Proteins as an Approach to Influenza Vaccines

    , JOURNAL OF VIROLOGY, Vol: 85, Pages: 3010-3014, ISSN: 0022-538X
  • Journal article
    Shelton H, Ayora-Talavera G, Ren J, Loureiro S, Pickles RJ, Barclay WS, Jones IMet al., 2011,

    Receptor Binding Profiles of Avian Influenza Virus Hemagglutinin Subtypes on Human Cells as a Predictor of Pandemic Potential

    , JOURNAL OF VIROLOGY, Vol: 85, Pages: 1875-1880, ISSN: 0022-538X

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