Publications

Search or filter publications

Search publications Search

Filter by type:

Filter by publication type

• Book
• Book chapter
• Conference paper
• Journal article
• Patent
• Report
• Software

Filter by year:

Filter from 202120202019201820172016201520142013201220112010200920082007200620052004200320022001 to Filter to 202120202019201820172016201520142013201220112010200920082007200620052004200320022001

---

Search results

• Journal article
  Singanayagam A, Zhou J, Elderfield RA, Frise R, Ashcroft J, Galiano M, Miah S, Nicolaou L, Barclay WSet al., 2020,

  Characterising viable virus from air exhaled by H1N1 influenza-infected ferrets reveals the importance of haemagglutinin stability for airborne infectivity

  , PLoS Pathogens, Vol: 16, Pages: 1-21, ISSN: 1553-7366

  The transmissibility and pandemic potential of influenza viruses depends on their ability to efficiently replicate and be released from an infected host, retain viability as they pass through the environment, and then initiate infection in the next host. There is a significant gap in knowledge about viral properties that enable survival of influenza viruses between hosts, due to a lack of experimental methods to reliably isolate viable virus from the air. Using a novel technique, we isolate and characterise infectious virus from droplets emitted by 2009 pandemic H1N1-infected ferrets. We demonstrate that infectious virus is predominantly released early after infection. A virus containing a mutation destabilising the haemagglutinin (HA) surface protein displayed reduced survival in air. Infectious virus recovered from droplets exhaled by ferrets inoculated with this virus contained mutations that conferred restabilisation of HA, indicating the importance of influenza HA stability for between-host survival. Using this unique approach can improve knowledge about the determinants and mechanisms of influenza transmissibility and ultimately could be applied to studies of airborne virus exhaled from infected people.

  • Abstract
  • Publisher Web Link
  • Open Access Link
  • Cite
• Journal article
  Mistry B, Long JS, Schreyer J, Staller E, Sanchez-David RY, Barclay WSet al., 2020,

  Elucidating the Interactions between Influenza Virus Polymerase and Host Factor ANP32A

  , JOURNAL OF VIROLOGY, Vol: 94, ISSN: 0022-538X
  • Author Web Link
  • Cite
  • Citations: 16
• Journal article
  Giotis ES, Carnell G, Young EF, Ghanny S, Soteropoulos P, Wang L-F, Barclay WS, Skinner MA, Temperton Net al., 2019,

  Entry of the bat influenza H17N10 virus into mammalian cells is enabled by the MHC class II HLA-DR receptor.

  , Nature Microbiology, Vol: 4, Pages: 2035-2038, ISSN: 2058-5276

  Haemagglutinin and neuraminidase surface glycoproteins of the bat influenza H17N10 virus neither bind to nor cleave sialic acid receptors, indicating that this virus employs cell entry mechanisms distinct from those of classical influenza A viruses. We observed that certain human haematopoietic cancer cell lines and canine MDCK II cells are susceptible to H17-pseudotyped viruses. We identified the human HLA-DR receptor as an entry mediator for H17 pseudotypes, suggesting that H17N10 possesses zoonotic potential.

  • Abstract
  • Publisher Web Link
  • Author Web Link
  • Open Access Link
  • Cite
• Journal article
  Goldhill DH, Lindsey B, Kugathasan R, Garza ZF, Jagne YJ, Sallah HJ, Goderski G, van Tol S, Höschler K, Meijer A, Barclay WS, de Silva TIet al., 2019,

  The Consequences of Egg Adaptation in the H3N2 Component to the Immunogenicity of Live Attenuated Influenza Vaccine

  <jats:title>Abstract</jats:title><jats:p>Adaptation in egg-passaged vaccine strains may cause reduced vaccine effectiveness due to altered antigenicity of the influenza haemagglutinin. We tested whether egg adaptation modified serum and mucosal antibody responses to the A(H3N2) component in the Live Attenuated Influenza Vaccine (LAIV). Twice as many children seroconverted to an egg-adapted H3N2 than the equivalent wildtype strain. Seroconversion to the wildtype strain was greater in children seronegative pre-LAIV, whereas higher mucosal IgA responses to wildtype antigen were observed if seropositive prior to vaccination. Sequencing of virus from nasopharyngeal swabs from 7 days post-LAIV showed low sequence diversity and no reversion of egg-adaptive mutations.</jats:p>

  • Abstract
  • Publisher Web Link
  • Cite
• Journal article
  Brown JC, Barclay WS, Galiano M, Harvey Ret al., 2019,

  Passage of influenza A/H3N2 viruses in human airway cells removes artefactual variants associated with neuraminidase-mediated binding.

  , Journal of General Virology, Vol: 101, Pages: 456-466, ISSN: 0022-1317

  Serological assays with modern influenza A/H3N2 viruses have become problematic due to the progressive reduction in the ability of viruses of this subtype to bind and agglutinate red blood cells (RBCs). This is due to reduced ability of the viral haemagglutinin (HA) glycoprotein to bind to the sialic acid-containing receptors presented by these cells. Additionally, as a result of reduced HA-mediated binding in cell culture, modern A/H3N2 viruses often acquire compensatory mutations during propagation that enable binding of cellular receptors through their neuraminidase (NA) surface protein. Viruses that have acquired this NA-mediated binding agglutinate RBCs through their NA, confusing the results of serological assays designed to assess HA antigenicity. Here we confirm with a large dataset that the acquisition of mutations that confer NA binding of RBCs is a culture artefact, and demonstrate that modern A/H3N2 isolates with acquired NA-binding mutations revert to a clinical-like NA sequence after a single passage in human airway epithelial (HAE) cells.

  • Abstract
  • Publisher Web Link
  • Author Web Link
  • Open Access Link
  • Cite
• Journal article
  Shah NM, Imami N, Kelleher P, Barclay WS, Johnson MRet al., 2019,

  Pregnancy-related immune suppression leads to altered influenza vaccine recall responses.

  , Clin Immunol, Vol: 208

  Pregnancy is a risk factor for severe influenza infection. Despite achieving seroprotective antibody titres post immunisation fewer pregnant women experience a reduction in influenza-like illness compared to non-pregnant cohorts. This may be due to the effects that immune-modulation in pregnancy has on vaccine efficacy leading to a less favourable immunologic response. To understand this, we investigated the antigen-specific cellular responses and leukocyte phenotype in pregnant and non-pregnant women who achieved seroprotection post immunisation. We show that pregnancy is associated with better antigen-specific inflammatory (IFN-γ) responses and an expansion of central memory T cells (Tcm) post immunisation, but low-level pregnancy-related immune regulation (HLA-G, PIBF) and associated reduced B-cell antibody maintenance (TGF-β) suggest poor immunologic responses compared to the non-pregnant. Thus far, studies of influenza vaccine immunogenicity have focused on the induction of antibodies but understanding additional vaccine-related cellular responses is needed to fully appreciate how pregnancy impacts on vaccine effectiveness.

  • Abstract
  • Author Web Link
  • Open Access Link
  • Cite
• Journal article
  Singanayagam A, Zambon M, Barclay W, 2019,

  Influenza virus with increased pH of HA activation has improved replication in cell culture but at the cost of infectivity in human airway epithelium.

  , Journal of Virology, Vol: 98, ISSN: 0022-538X

  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

  • Abstract
  • Author Web Link
  • Open Access Link
  • Cite
• Journal article
  Staller E, Sheppard CM, Neasham PJ, Mistry B, Peacock TP, Goldhill DH, Long JS, Barclay WSet al., 2019,

  ANP32 proteins are essential for influenza virus replication in human cells

  , Journal of Virology, Vol: 93, ISSN: 0022-538X

  ANP32 proteins have been implicated in supporting influenza virus replication, but most of the work to date has focused on the ability of avian Anp32 proteins to overcome restriction of avian influenza polymerases in human cells. Using a CRISPR approach we show that human ANP32A and ANP32B are functionally redundant but essential host factors for mammalian-adapted influenza A virus (IAV) and influenza B virus (IBV) replication in human cells. When both proteins are absent from human cells, influenza polymerases are unable to replicate the viral genome, and infectious virus cannot propagate. Provision of exogenous ANP32A or –B recovers polymerase activity and virus growth. We demonstrate that this redundancy is absent in the murine Anp32 orthologues: murine Anp32A is incapable of recovering IAV polymerase activity, while murine Anp32B can. Intriguingly, IBV polymerase is able to use murine Anp32A. We show using a domain swap and point mutations that the LRR 5 region comprises an important functional domain for mammalian ANP32 proteins. Our approach has identified a pair of essential host factors for influenza virus replication and can be harnessed to inform future interventions.

  • Abstract
  • Open Access Link
  • Cite
• Journal article
  Peacock TP, Sheppard CM, Staller E, Barclay WSet al., 2019,

  Host Determinants of Influenza RNA Synthesis.

  , Annu Rev Virol

  Influenza viruses are a leading cause of seasonal and pandemic respiratory illness. Influenza is a negative-sense single-stranded RNA virus that encodes its own RNA-dependent RNA polymerase (RdRp) for nucleic acid synthesis. The RdRp catalyzes mRNA synthesis, as well as replication of the virus genome (viral RNA) through a complementary RNA intermediate. Virus propagation requires the generation of these RNA species in a controlled manner while competing heavily with the host cell for resources. Influenza virus appropriates host factors to enhance and regulate RdRp activity at every step of RNA synthesis. This review describes such host factors and summarizes our current understanding of the roles they play in viral synthesis of RNA. Expected final online publication date for the Annual Review of Virology Volume 6 is September 30, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  • Abstract
  • Author Web Link
  • Cite
• Journal article
  Lindsey BB, Jagne YJ, Armitage EP, Singanayagam A, Sallah HJ, Drammeh S, Senghore E, Mohammed NI, Jeffries D, Höschler K, Tregoning JS, Meijer A, Clarke E, Dong T, Barclay W, Kampmann B, de Silva TIet al., 2019,

  Effect of a Russian-backbone live-attenuated influenza vaccine with an updated pandemic H1N1 strain on shedding and immunogenicity among children in The Gambia: an open-label, observational, phase 4 study

  , Lancet Respiratory Medicine, Vol: 7, Pages: 665-676, ISSN: 2213-2600

  BACKGROUND: The efficacy and effectiveness of the pandemic H1N1 (pH1N1) component in live attenuated influenza vaccine (LAIV) is poor. The reasons for this paucity are unclear but could be due to impaired replicative fitness of pH1N1 A/California/07/2009-like (Cal09) strains. We assessed whether an updated pH1N1 strain in the Russian-backbone trivalent LAIV resulted in greater shedding and immunogenicity compared with LAIV with Cal09. METHODS: We did an open-label, prospective, observational, phase 4 study in Sukuta, a periurban area in The Gambia. We enrolled children aged 24-59 months who were clinically well. Children received one dose of the WHO prequalified Russian-backbone trivalent LAIV containing either A/17/California/2009/38 (Cal09) or A/17/New York/15/5364 (NY15) based on their year of enrolment. Primary outcomes were the percentage of children with LAIV strain shedding at day 2 and day 7, haemagglutinin inhibition seroconversion, and an increase in influenza haemagglutinin-specific IgA and T-cell responses at day 21 after LAIV. This study is nested within a randomised controlled trial investigating LAIV-microbiome interactions (NCT02972957). FINDINGS: Between Feb 8, 2017, and April 12, 2017, 118 children were enrolled and received one dose of the Cal09 LAIV from 2016-17. Between Jan 15, 2018, and March 28, 2018, a separate cohort of 135 children were enrolled and received one dose of the NY15 LAIV from 2017-18, of whom 126 children completed the study. Cal09 showed impaired pH1N1 nasopharyngeal shedding (16 of 118 children [14%, 95% CI 8·0-21·1] with shedding at day 2 after administration of LAIV) compared with H3N2 (54 of 118 [46%, 36·6-55·2]; p<0·0001) and influenza B (95 of 118 [81%, 72·2-87·2]; p<0·0001), along with suboptimal serum antibody (seroconversion in six of 118 [5%, 1·9-10·7]) and T-cell responses (CD4+ interferon γ-positive and/or CD4+ interleukin 2-positive

  • Abstract
  • Publisher Web Link
  • Author Web Link
  • Open Access Link
  • Cite

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.