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  • Journal article
    Shelton H, Smith M, Hartgroves L, Stilwell P, Roberts K, Johnson B, Barclay Wet al., 2012,

    An influenza reassortant with polymerase of pH1N1 and NS gene of H3N2 influenza A virus is attenuated in vivo

    , JOURNAL OF GENERAL VIROLOGY, Vol: 93, Pages: 998-1006, ISSN: 0022-1317
  • Journal article
    Buettner M, Lang A, Tudor CS, Meyer B, Cruchley A, Barros MHM, Farrell PJ, Jaeck H-M, Schuh W, Niedobitek Get al., 2012,

    Lytic Epstein-Barr virus infection in epithelial cells but not in B-lymphocytes is dependent on Blimp1

    , JOURNAL OF GENERAL VIROLOGY, Vol: 93, Pages: 1059-1064, ISSN: 0022-1317
  • 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 Pet 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
    White RE, Raemer PC, Naresh KN, Meixlsperger S, Pinaud L, Rooney C, Savoldo B, Coutinho R, Boedoer C, Gribben J, Ibrahim HA, Bower M, Nourse JP, Gandhi MK, Middeldorp J, Cader FZ, Murray P, Muenz C, Allday MJet al., 2012,

    EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors

    , JOURNAL OF CLINICAL INVESTIGATION, Vol: 122, Pages: 1487-1502, ISSN: 0021-9738
  • 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
  • Journal article
    Tzartos JS, Khan G, Vossenkamper A, Cruz-Sadaba M, Lonardi S, Sefia E, Meager A, Elia A, Middeldorp JM, Clemens M, Farrell PJ, Giovannoni G, Meier U-Cet al., 2012,

    Association of innate immune activation with latent Epstein-Barr virus in active MS lesions

    , NEUROLOGY, Vol: 78, Pages: 15-23, ISSN: 0028-3878

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