Publications
316 results found
Long J, Efstathios SG, Moncorge O, et al., 2016, Species difference in ANP32A underlies influenza A virus polymerase host restriction, Nature, Vol: 529, Pages: 101-104, ISSN: 1476-4687
Influenza pandemics occur unpredictably when zoonotic influenza viruses with novel antigenicity acquire the ability to transmit amongst humans1. Host range breaches are limited by incompatibilities between avian virus components and the human host. Barriers include receptor preference, virion stability and poor activity of the avian virus RNA-dependent RNA polymerase in human cells2. Mutants of the heterotrimeric viral polymerase components, particularly PB2 protein, are selected during mammalian adaptation, but their mode of action is unknown3, 4, 5, 6. We show that a species-specific difference in host protein ANP32A accounts for the suboptimal function of avian virus polymerase in mammalian cells. Avian ANP32A possesses an additional 33 amino acids between the leucine-rich repeats and carboxy-terminal low-complexity acidic region domains. In mammalian cells, avian ANP32A rescued the suboptimal function of avian virus polymerase to levels similar to mammalian-adapted polymerase. Deletion of the avian-specific sequence from chicken ANP32A abrogated this activity, whereas its insertion into human ANP32A, or closely related ANP32B, supported avian virus polymerase function. Substitutions, such as PB2(E627K), were rapidly selected upon infection of humans with avian H5N1 or H7N9 influenza viruses, adapting the viral polymerase for the shorter mammalian ANP32A. Thus ANP32A represents an essential host partner co-opted to support influenza virus replication and is a candidate host target for novel antivirals.
Koutsakos M, Thi HN, Barclay WS, et al., 2015, Knowns and unknowns of influenza B viruses, Future Microbiology, Vol: 11, Pages: 119-135, ISSN: 1746-0913
Influenza B viruses (IBVs) circulate annually along with influenza A (IAV) strains during seasonal epidemics. IBV can dominate influenza seasons and cause severe disease, particularly in children and adolescents. Research has revealed interesting aspects of IBV and highlighted the importance of these viruses in clinical settings. Yet, many important questions remain unanswered. In this review, the clinical relevance of IBV is emphasized, unique features in epidemiology, host range and virology are highlighted and gaps in knowledge pinpointed. Multiple aspects of IBV epidemiology, evolution, virology and immunology are discussed. Future research into IBV is needed to understand how we can prevent severe disease in high-risk groups, especially children and elderly.
Matos-Patron A, Byrd-Leotis L, Steinhauer DA, et al., 2015, Amino acid substitution D222N from fatal influenza infection affects receptor-binding properties of the influenza A(H1N1)pdm09 virus, VIROLOGY, Vol: 484, Pages: 15-21, ISSN: 0042-6822
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- Citations: 10
Liu M, Lam MK-H, Zhang Q, et al., 2015, The Functional Study of the N-Terminal Region of Influenza B Virus Nucleoprotein, PLOS One, Vol: 10, ISSN: 1932-6203
Influenza nucleoprotein (NP) is a major component of the ribonucleoprotein (vRNP) in influenzavirus, which functions for the transcription and replication of viral genome. Comparedto the nucleoprotein of influenza A (ANP), the N-terminal region of influenza B nucleoprotein(BNP) is much extended. By virus reconstitution, we found that the first 38 residues areessential for viral growth. We further illustrated the function of BNP by mini-genome reconstitution,fluorescence microscopy, electron microscopy, light scattering and gel shift.Results show that the N terminus is involved in the formation of both higher homo-oligomersof BNP and BNP-RNA complex.
Elderfield RA, Parker L, Stilwell P, et al., 2015, Ferret airway epithelial cell cultures support efficient replication of influenza B virus but not mumps virus, JOURNAL OF GENERAL VIROLOGY, Vol: 96, Pages: 2092-2098, ISSN: 0022-1317
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- Citations: 5
Long JS, Benfield CT, Barclay WS, 2015, One-way trip: Influenza virus' adaptation to gallinaceous poultry may limit its pandemic potential (vol 37, pg 204, 2015), BIOESSAYS, Vol: 37, Pages: 463-463, ISSN: 0265-9247
Long J, Wright E, Molesti E, et al., 2015, Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry., F1000 Research, Vol: 4, Pages: 30-30, ISSN: 2046-1402
Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achieved in vivo. We propose CQ as a priority candidate to consider for treatment of EBOV.
Long J, Wright E, Molesti E, et al., 2015, Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry, F1000Research, Vol: 4, ISSN: 2046-1402
Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achieved in vivo. We propose CQ as a priority candidate to consider for treatment of EBOV.
Almond MH, Bakhsoliani E, Edwards MR, et al., 2015, Obesity Is Associated With Decreased Expression Of Suppressor Of Cytokine Signalling 3 In Human Alveolar Macrophages, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Long JS, Benfield CT, Barclay WS, 2014, One-way trip: Influenza virus' adaptation to gallinaceous poultry may limit its pandemic potential, Bioessays, Vol: 37, Pages: 204-212, ISSN: 1521-1878
We hypothesise that some influenza virus adaptations to poultry may explain why the barrier for human-to-human transmission is not easily overcome once the virus has crossed from wild birds to chickens. Since the cluster of human infections with H5N1 influenza in Hong Kong in 1997, chickens have been recognized as the major source of avian influenza virus infection in humans. Although often severe, these infections have been limited in their subsequent human-to-human transmission, and the feared H5N1 pandemic has not yet occurred. Here we examine virus adaptations selected for during replication in chickens and other gallinaceous poultry. These include altered receptor binding and increased pH of fusion of the haemagglutinin as well as stalk deletions of the neuraminidase protein. This knowledge could aid the delivery of vaccines and increase our ability to prioritize research efforts on those viruses from the diverse array of avian influenza viruses that have greatest human pandemic potential.
Elderfield RA, Watson SJ, Godlee A, et al., 2014, Accumulation of human-adapting mutations during circulation of A(H1N1)pdm09 influenza virus in humans in the United Kingdom., Journal of virology, Vol: 88, Pages: 13269-13283, ISSN: 0022-538X
<h4>Unlabelled</h4>The influenza pandemic that emerged in 2009 provided an unprecedented opportunity to study adaptation of a virus recently acquired from an animal source during human transmission. In the United Kingdom, the novel virus spread in three temporally distinct waves between 2009 and 2011. Phylogenetic analysis of complete viral genomes showed that mutations accumulated over time. Second- and third-wave viruses replicated more rapidly in human airway epithelial (HAE) cells than did the first-wave virus. In infected mice, weight loss varied between viral isolates from the same wave but showed no distinct pattern with wave and did not correlate with viral load in the mouse lungs or severity of disease in the human donor. However, second- and third-wave viruses induced less alpha interferon in the infected mouse lungs. NS1 protein, an interferon antagonist, had accumulated several mutations in second- and third-wave viruses. Recombinant viruses with the third-wave NS gene induced less interferon in human cells, but this alone did not account for increased virus fitness in HAE cells. Mutations in HA and NA genes in third-wave viruses caused increased binding to α-2,6-sialic acid and enhanced infectivity in human mucus. A recombinant virus with these two segments replicated more efficiently in HAE cells. A mutation in PA (N321K) enhanced polymerase activity of third-wave viruses and also provided a replicative advantage in HAE cells. Therefore, multiple mutations allowed incremental changes in viral fitness, which together may have contributed to the apparent increase in severity of A(H1N1)pdm09 influenza virus during successive waves.<h4>Importance</h4>Although most people infected with the 2009 pandemic influenza virus had mild or unapparent symptoms, some suffered severe and devastating disease. The reasons for this variability were unknown, but the numbers of severe cases increased during successive waves of human infection i
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- Citations: 59
Jia N, Barclay WS, Roberts K, et al., 2014, Glycomic characterization of respiratory tract tissues of ferrets IMPLICATIONS FOR ITS USE IN INFLUENZA VIRUS INFECTION STUDIES, Journal of Biological Chemistry, Vol: 289, Pages: 28489-28504, ISSN: 0021-9258
The initial recognition between influenza virus and the host cell is mediated by interactions between the viral surface protein hemagglutinin and sialic acid-terminated glycoconjugates on the host cell surface. The sialic acid residues can be linked to the adjacent monosaccharide by α2–3- or α2–6-type glycosidic bonds. It is this linkage difference that primarily defines the species barrier of the influenza virus infection with α2–3 binding being associated with avian influenza viruses and α2–6 binding being associated with human strains. The ferret has been extensively used as an animal model to study the transmission of influenza. To better understand the validity of this model system, we undertook glycomic characterization of respiratory tissues of ferret, which allows a comparison of potential viral receptors to be made between humans and ferrets. To complement the structural analysis, lectin staining experiments were performed to characterize the regional distributions of glycans along the respiratory tract of ferrets. Finally, the binding between the glycans identified and the hemagglutinins of different strains of influenza viruses was assessed by glycan array experiments. Our data indicated that the respiratory tissues of ferret heterogeneously express both α2–3- and α2–6-linked sialic acids. However, the respiratory tissues of ferret also expressed the Sda epitope (NeuAcα2-3(GalNAcβ1–4)Galβ1–4GlcNAc) and sialylated N,N′-diacetyllactosamine (NeuAcα2–6GalNAcβ1–4GlcNAc), which have not been observed in the human respiratory tract surface epithelium. The presence of the Sda epitope reduces potential binding sites for avian viruses and thus may have implications for the usefulness of the ferret in the study of influenza virus infection.
Goujon C, Moncorge O, Bauby H, et al., 2014, Transfer of the Amino-Terminal Nuclear Envelope Targeting Domain of Human MX2 Converts MX1 into an HIV-1 Resistance Factor, JOURNAL OF VIROLOGY, Vol: 88, Pages: 9017-9026, ISSN: 0022-538X
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- Citations: 70
Cauldwell AV, Long JS, Moncorge O, et al., 2014, Viral determinants of influenza A virus host range, JOURNAL OF GENERAL VIROLOGY, Vol: 95, Pages: 1193-1210, ISSN: 0022-1317
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- Citations: 109
Marriott AC, Dove BK, Whittaker CJ, et al., 2014, Low Dose Influenza Virus Challenge in the Ferret Leads to Increased Virus Shedding and Greater Sensitivity to Oseltamivir, PLOS ONE, Vol: 9, ISSN: 1932-6203
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- Citations: 35
Macdonald DC, Singh H, Whelan MA, et al., 2014, Harnessing alveolar macrophages for sustained mucosal T-cell recall confers long-term protection to mice against lethal influenza challenge without clinical disease, MUCOSAL IMMUNOLOGY, Vol: 7, Pages: 89-100, ISSN: 1933-0219
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- Citations: 16
Goujon C, Moncorge O, Bauby H, et al., 2013, Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection, NATURE, Vol: 502, Pages: 559-+, ISSN: 0028-0836
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- Citations: 426
Blumenkrantz D, Roberts KL, Shelton H, et al., 2013, The Short Stalk Length of Highly Pathogenic Avian Influenza H5N1 Virus Neuraminidase Limits Transmission of Pandemic H1N1 Virus in Ferrets, JOURNAL OF VIROLOGY, Vol: 87, Pages: 10539-10551, ISSN: 0022-538X
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- Citations: 60
Sridhar S, Begom S, Bermingham A, et al., 2013, Cellular immune correlates of protection against symptomatic pandemic influenza, Nature Medicine, Vol: n/a, ISSN: 1078-8956
Long JS, Howard WA, Nunez A, et al., 2013, The Effect of the PB2 Mutation 627K on Highly Pathogenic H5N1 Avian Influenza Virus Is Dependent on the Virus Lineage, JOURNAL OF VIROLOGY, Vol: 87, Pages: 9983-9996, ISSN: 0022-538X
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- Citations: 43
Almond MH, Edwards MR, Barclay WS, et al., 2013, Obesity and susceptibility to severe outcomes following respiratory viral infection, THORAX, Vol: 68, Pages: 684-686, ISSN: 0040-6376
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- Citations: 57
Shelton H, Roberts KL, Molesti E, et al., 2013, Mutations in haemagglutinin that affect receptor binding and pH stability increase replication of a PR8 influenza virus with H5 HA in the upper respiratory tract of ferrets and may contribute to transmissibility, JOURNAL OF GENERAL VIROLOGY, Vol: 94, Pages: 1220-1229, ISSN: 0022-1317
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- Citations: 51
Bhatt S, Lam TT, Lycett SJ, et al., 2013, The evolutionary dynamics of influenza A virus adaptation to mammalian hosts, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 368, ISSN: 0962-8436
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- Citations: 37
Fouchier RAM, Garcia-Sastre A, Kawaoka Y, et al., 2013, Transmission Studies Resume For Avian Flu, SCIENCE, Vol: 339, Pages: 520-521, ISSN: 0036-8075
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- Citations: 26
Cauldwell AV, Moncorge O, Barclay WS, 2013, Unstable Polymerase-Nucleoprotein Interaction Is Not Responsible for Avian Influenza Virus Polymerase Restriction in Human Cells, JOURNAL OF VIROLOGY, Vol: 87, Pages: 1278-1284, ISSN: 0022-538X
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- Citations: 35
Moncorge O, Long JS, Cauldwell AV, et al., 2013, Investigation of Influenza Virus Polymerase Activity in Pig Cells, JOURNAL OF VIROLOGY, Vol: 87, Pages: 384-394, ISSN: 0022-538X
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- Citations: 38
Ito K, Ashcroft J, Brookes D, et al., 2013, Inhibitory Effects Of Rv1088, A Narrow Spectrum Kinase Inhibitor, On Cytokine Production In Response To Pandemic Flu Infections Of Primary Respiratory Cell Cultures, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 187, ISSN: 1073-449X
Sridhar S, Begom S, Bermingham A, et al., 2012, Predominance of heterosubtypic IFN-?-only-secreting effector memory T cells in pandemic H1N1 naive adults, EUROPEAN JOURNAL OF IMMUNOLOGY, Vol: 42, Pages: 2913-2924, ISSN: 0014-2980
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- Citations: 28
Williamson SM, Tucker AW, McCrone IS, et al., 2012, Descriptive clinical and epidemiological characteristics of influenza A H1N1 2009 virus infections in pigs in England, VETERINARY RECORD, Vol: 171, Pages: 271-U47, ISSN: 0042-4900
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- Citations: 20
Roberts KL, Shelton H, Stilwell P, et al., 2012, Transmission of a 2009 H1N1 Pandemic Influenza Virus Occurs before Fever Is Detected, in the Ferret Model, PLOS ONE, Vol: 7, ISSN: 1932-6203
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- Citations: 32
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