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
    Atchison C, Pristerà P, Cooper E, Papageorgiou V, Redd R, Piggin M, Flower B, Fontana G, Satkunarajah S, Ashrafian H, Lawrence-Jones A, Naar L, Chigwende J, Gibbard S, Riley S, Darzi A, Elliott P, Ashby D, Barclay W, Cooke GS, Ward Het al., 2020,

    Usability and acceptability of home-based self-testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibodies for population surveillance

    , Clinical Infectious Diseases, Vol: 2020, Pages: 1-10, ISSN: 1058-4838

    BACKGROUND: This study assesses acceptability and usability of home-based self-testing for SARS-CoV-2 antibodies using lateral flow immunoassays (LFIA). METHODS: We carried out public involvement and pilot testing in 315 volunteers to improve usability. Feedback was obtained through online discussions, questionnaires, observations and interviews of people who tried the test at home. This informed the design of a nationally representative survey of adults in England using two LFIAs (LFIA1 and LFIA2) which were sent to 10,600 and 3,800 participants, respectively, who provided further feedback. RESULTS: Public involvement and pilot testing showed high levels of acceptability, but limitations with the usability of kits. Most people reported completing the test; however, they identified difficulties with practical aspects of the kit, particularly the lancet and pipette, a need for clearer instructions and more guidance on interpretation of results. In the national study, 99.3% (8,693/8,754) of LFIA1 and 98.4% (2,911/2,957) of LFIA2 respondents attempted the test and 97.5% and 97.8% of respondents completed it, respectively. Most found the instructions easy to understand, but some reported difficulties using the pipette (LFIA1: 17.7%) and applying the blood drop to the cassette (LFIA2: 31.3%). Most respondents obtained a valid result (LFIA1: 91.5%; LFIA2: 94.4%). Overall there was substantial concordance between participant and clinician interpreted results (kappa: LFIA1 0.72; LFIA2 0.89). CONCLUSION: Impactful public involvement is feasible in a rapid response setting. Home self-testing with LFIAs can be used with a high degree of acceptability and usability by adults, making them a good option for use in seroprevalence surveys.

  • Journal article
    Scott C, Kankanala J, Foster TL, Goldhill DH, Bao P, Simmons K, Pingen M, Bentham M, Atkins E, Loundras E, Eldertield R, Claridge JK, Thompson J, Stilwell PR, Tathineni R, McKimmie CS, Targett-Adams P, Schnell JR, Cook GP, Evans S, Barclay WS, Foster R, Griffin Set al., 2020,

    Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza

    , PLOS PATHOGENS, Vol: 16, ISSN: 1553-7366
  • Journal article
    Sanchez-David RY, Swann OC, Peacock TP, Barclay WSet al., 2020,

    ACE2: The Only Thing That Matters?

    , AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 202, Pages: 161-163, ISSN: 1073-449X
  • Journal article
    McKay PF, Hu K, Blakney AK, Samnuan K, Brown JC, Penn R, Zhou J, Bouton CR, Rogers P, Polra K, Lin PJC, Barbosa C, Tam YK, Barclay WS, Shattock RJet al., 2020,

    Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice

    , Nature Communications, Vol: 11, Pages: 1-7, ISSN: 2041-1723

    The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-γ production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.

  • Journal article
    Zhou J, Otter JA, Price JR, Cimpeanu C, Garcia DM, Kinross J, Boshier PR, Mason S, Bolt F, Holmes AH, Barclay WSet al., 2020,

    Investigating SARS-CoV-2 surface and air contamination in an acute healthcare setting during the peak of the COVID-19 pandemic in London

    , Clinical Infectious Diseases, Vol: 2020, Pages: 1-1, ISSN: 1058-4838

    BACKGROUND: Evaluation of SARS-CoV-2 surface and air contamination during the COVID-19 pandemic in London. METHODS: We performed this prospective cross-sectional observational study in a multi-site London hospital. Air and surface samples were collected from seven clinical areas, occupied by patients with COVID-19, and a public area of the hospital. Three or four 1.0 m3 air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected by RT-qPCR and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined. RESULTS: Viral RNA was detected on 114/218 (52.3%) of surfaces and 14/31 (38.7%) air samples but no virus was cultured. The proportion of surface samples contaminated with viral RNA varied by item sampled and by clinical area. Viral RNA was detected on surfaces and in air in public areas of the hospital but was more likely to be found in areas immediately occupied by COVID-19 patients than in other areas (67/105 (63.8%) vs. 29/64 (45.3%) (odds ratio 0.5, 95% confidence interval 0.2-0.9, p=0.025, Chi squared test)). The high PCR Ct value for all samples (>30) indicated that the virus would not be culturable. CONCLUSIONS: Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from environmental contamination in managing COVID-19, and the need for effective use of PPE, physical distancing, and hand/surface hygiene.

  • Journal article
    Rodriguez-Manzano J, Malpartida-Cardenas K, Moser N, Pennisi I, Cavuto M, Miglietta L, Moniri A, Penn R, Satta G, Randell P, Davies F, Bolt F, Barclay W, Holmes A, Georgiou Pet al., 2020,

    A handheld point-of-care system for rapid detection of SARS-CoV-2 in under 20 minutes

    <jats:title>Abstract</jats:title><jats:p>The COVID-19 pandemic is a global health emergency characterized by the high rate of transmission and ongoing increase of cases globally. Rapid point-of-care (PoC) diagnostics to detect the causative virus, SARS-CoV-2, are urgently needed to identify and isolate patients, contain its spread and guide clinical management. In this work, we report the development of a rapid PoC diagnostic test (&lt; 20 min) based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) and semiconductor technology for the detection of SARS-CoV-2 from extracted RNA samples. The developed LAMP assay was tested on a real-time benchtop instrument (RT-qLAMP) showing a lower limit of detection of 10 RNA copies per reaction. It was validated against 183 clinical samples including 127 positive samples (screened by the CDC RT-qPCR assay). Results showed 90.55% sensitivity and 100% specificity when compared to RT-qPCR and average positive detection times of 15.45 ± 4.43 min. For validating the incorporation of the RT-LAMP assay onto our PoC platform (RT-eLAMP), a subset of samples was tested (n=40), showing average detection times of 12.89 ± 2.59 min for positive samples (n=34), demonstrating a comparable performance to a benchtop commercial instrument. Paired with a smartphone for results visualization and geo-localization, this portable diagnostic platform with secure cloud connectivity will enable real-time case identification and epidemiological surveillance.</jats:p><jats:sec><jats:title>One Sentence Summary</jats:title><jats:p>We demonstrate isothermal detection of SARS-CoV-2 in under 20 minutes from extracted RNA samples with a handheld Lab-on-Chip platform.</jats:p></jats:sec>

  • Journal article
    Peacock TP, Swann OC, Salvesen HA, Staller E, Leung PB, Goldhill DH, Zhou H, Lillico SG, Whitelaw CBA, Long JS, Barclay WSet al., 2020,

    Swine ANP32A supports avian influenza virus polymerase.

    , Journal of Virology, Vol: 94, ISSN: 0022-538X

    Avian influenza viruses occasionally infect and adapt to mammals, including humans. Swine are often described as 'mixing vessels', being susceptible to both avian and human origin viruses, which allows the emergence of novel reassortants, such as the precursor to the 2009 H1N1 pandemic. ANP32 proteins are host factors that act as influenza virus polymerase cofactors. In this study we describe how swine ANP32A, uniquely among the mammalian ANP32 proteins tested, supports activity of avian origin influenza virus polymerases, and avian influenza virus replication. We further show that after the swine-origin influenza virus emerged in humans and caused the 2009 pandemic it evolved polymerase gene mutations that enabled it to more efficiently use human ANP32 proteins. We map the enhanced pro-viral activity of swine ANP32A to a pair of amino acids, 106 and 156, in the leucine-rich repeat and central domains and show these mutations enhance binding to influenza virus trimeric polymerase. These findings help elucidate the molecular basis for the 'mixing vessel' trait of swine and further our understanding of the evolution and ecology of viruses in this host.Importance Avian influenza viruses can jump from wild birds and poultry into mammalian species such as humans or swine, but only continue to transmit if they accumulate mammalian adapting mutations. Pigs appear uniquely susceptible to both avian and human strains of influenza and are often described as virus 'mixing vessels'. In this study, we describe how a host factor responsible for regulating virus replication, ANP32A, is different between swine and humans. Swine ANP32A allows a greater range of influenza viruses, specifically those from birds, to replicate. It does this through binding the virus polymerase more tightly than the human version of the protein. This work helps to explain the unique properties of swine as 'mixing vessels'.

  • Journal article
    Kellam P, Barclay W, 2020,

    The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection

    , Journal of General Virology, Vol: 101, ISSN: 0022-1317

    SARS-CoV-2 is a novel coronavirus that is the causative agent of coronavirus infectious disease 2019 (COVID-19). As of 17 April 2020, it has infected 2 114 269 people, resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed, studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.

  • Journal article
    Staller E, Baillon L, Frise R, Peacock T, Sheppard C, Sancho-Shimizu V, Barclay Wet al., 2020,

    A rare variant in ANP32B impairs influenza virus replication in human cells

    , biorxiv

    Viruses require host factors to support their replication, and genetic variation in such factors can affect susceptibility to infectious disease. Influenza virus replication in human cells relies on ANP32 proteins, which are involved in assembly of replication-competent dimeric influenza virus polymerase (FluPol) complexes. Here, we investigate naturally occurring single nucleotide variants (SNV) in the human Anp32A and Anp32B genes. We note that variant rs182096718 in Anp32B is found at a higher frequency than other variants in either gene. This SNV results in a D130A substitution in ANP32B, which is less able to support FluPol activity than wildtype ANP32B and binds FluPol with lower affinity. Interestingly, ANP32B-D130A exerts a dominant negative effect over wildtype ANP32B and interferes with the functionally redundant paralogue ANP32A. FluPol activity and virus replication are attenuated in CRISPR-edited cells expressing wildtype ANP32A and mutant ANP32B-D130A. We propose a model in which the D130A mutation impairs FluPol dimer formation, thus resulting in compromised replication. We suggest that both homozygous and heterozygous carriers of rs182096718 may have some genetic protection against influenza viruses.

  • Journal article
    Lee LYY, Zhou J, Frise R, Goldhill DH, Koszalka P, Mifsud EJ, Baba K, Noda T, Ando Y, Sato K, Yuki A-I, Shishido T, Uehara T, Wildum S, Zwanziger E, Collinson N, Kuhlbusch K, Clinch B, Hurt AC, Barclay WSet al., 2020,

    Baloxavir treatment of ferrets infected with influenza A(H1N1)pdm09 virus reduces onward transmission

    , PLOS PATHOGENS, Vol: 16, ISSN: 1553-7366

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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