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Journal articleElderfield 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: 60
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Journal articleKwok KO, Cowling BJ, Wei VWI, et al., 2014,
Social contacts and the locations in which they occur as risk factors for influenza infection
, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 281, ISSN: 0962-8452- Author Web Link
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- Citations: 34
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Journal articleRoy A, Eisenhut M, Harris RJ, et al., 2014,
Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis
, BMJ: British Medical Journal, Vol: 349, ISSN: 0959-535XObjectives To determine whether BCG vaccination protects against Mycobacterium tuberculosis infection as assessed by interferon γ release assays (IGRA) in children.Design Systematic review and meta-analysis. Searches of electronic databases 1950 to November 2013, checking of reference lists, hand searching of journals, and contact with experts.Setting Community congregate settings and households.Inclusion criteria Vaccinated and unvaccinated children aged under 16 with known recent exposure to patients with pulmonary tuberculosis. Children were screened for infection with M tuberculosis with interferon γ release assays.Data extraction Study results relating to diagnostic accuracy were extracted and risk estimates were combined with random effects meta-analysis.Results The primary analysis included 14 studies and 3855 participants. The estimated overall risk ratio was 0.81 (95% confidence interval 0.71 to 0.92), indicating a protective efficacy of 19% against infection among vaccinated children after exposure compared with unvaccinated children. The observed protection was similar when estimated with the two types of interferon γ release assays (ELISpot or QuantiFERON). Restriction of the analysis to the six studies (n=1745) with information on progression to active tuberculosis at the time of screening showed protection against infection of 27% (risk ratio 0.73, 0.61 to 0.87) compared with 71% (0.29, 0.15 to 0.58) against active tuberculosis. Among those infected, protection against progression to disease was 58% (0.42, 0.23 to 0.77).Conclusions BCG protects against M tuberculosis infection as well as progression from infection to disease.
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Journal articleGoujon 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- Author Web Link
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- Citations: 70
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Journal articleRead JM, Lessler J, Riley S, et al., 2014,
Social mixing patterns in rural and urban areas of southern China
, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 281, ISSN: 0962-8452- Author Web Link
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- Citations: 101
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Journal articleCauldwell 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- Author Web Link
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- Citations: 109
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Conference paperGoritzka M, Durant LR, Pereira C, et al., 2014,
Interferon-a/b receptor signalling is amplifying early proinflammatory cytokine production in the lung during Respiratory Syncytial Virus (RSV) infection
, Annual Congress of the British-Society-for-Immunology, Publisher: Wiley, Pages: 6128-6136, ISSN: 0019-2805Type I interferons (IFNs) are produced early upon virus infection and signal through the alpha/beta interferon (IFN-/) receptor(IFNAR) to induce genes that encode proteins important for limiting viral replication and directing immune responses. Toinvestigate the extent to which type I IFNs play a role in the local regulation of inflammation in the airways, we examined theirimportance in early lung responses to infection with respiratory syncytial virus (RSV). IFNAR1-deficient (IFNAR1 / ) mice displayedincreased lung viral load and weight loss during RSV infection. As expected, expression of IFN-inducible genes was markedlyreduced in the lungs of IFNAR1 / mice. Surprisingly, we found that the levels of proinflammatory cytokines and chemokinesin the lungs of RSV-infected mice were also greatly reduced in the absence of IFNAR signaling. Furthermore, low levels ofproinflammatory cytokines were also detected in the lungs of IFNAR1 / mice challenged with noninfectious innate immunestimuli such as selected Toll-like receptor (TLR) agonists. Finally, recombinant IFN- was sufficient to potentiate the productionof inflammatory mediators in the lungs of wild-type mice challenged with innate immune stimuli. Thus, in addition to itswell-known role in antiviral resistance, type I IFN receptor signaling acts as a central driver of early proinflammatory responsesin the lung. Inhibiting the effects of type I IFNs may therefore be useful in dampening inflammation in lung diseases characterizedby enhanced inflammatory cytokine production.
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Journal articleDhasmana DJ, Ross C, Bradley C, et al., 2014,
Performance of Xpert MTB/RIF in the diagnosis of tuberculous mediastinal lymphadenopathy by endobronchial ultrasound.
, Annals of the American Thoracic Society, Vol: 11, Pages: 392-396, ISSN: 2329-6933RATIONALE: The Xpert (GeneXpert) MTB/RIF, an integrated polymerase chain reaction assay, has not been systematically studied in extrapulmonary and in particular mediastinal tuberculosis (TB). OBJECTIVES: To investigate the performance of Xpert MTB/RIF in the diagnosis of intrathoracic nodal TB in a large tertiary urban medical center in the UK. METHODS: We collected clinical, cytological, and microbiological data from two cohorts: 116 consecutive patients referred with mediastinal lymphadenopathy with detailed diagnostic information obtained, and an immediately subsequent second cohort of 52 consecutive patients with microbiologically confirmed mediastinal TB lymphadenopathy. All data were derived between January 2010 and October 2012. All patients underwent endobronchial ultrasound and transbronchial needle aspiration (TBNA). The performance of a single Xpert MTB/RIF assay alongside standard investigations, cytology, and microscopy/culture was evaluated against culture-confirmed TB. MEASUREMENTS AND MAIN RESULTS: Microbiologically confirmed TB mediastinal lymphadenopathy was diagnosed in a total of 88 patients from both cohorts. Three culture-negative cases with associated caseating granulomatous inflammation on TBNA were given a probable diagnosis. A single Xpert MTB/RIF assay demonstrated overall sensitivity for culture-positive TB of 72.6% (62.3-81.0%). Xpert specificity from cohort 1 was 96.3% (89.1-99.1%). The positive predictive value was 88.9% (69.7-97.1%), negative predictive value was 86.5% (76.9-92.1%), and odds ratio was 51.3 (24.0-98.0) for correctly identifying culture-positive disease. Xpert captured all microscopy-positive cases (14 of 14) and the majority of microscopy-negative cases (48 of 71, 67.6%). Among the cases that were culture positive by TBNA, Xpert identified two-thirds of the multiple drug-resistant TB cases, leading to immediate regimen change up to 5 weeks ahead of positive cultures. The use of Xpert combined with cytology increased th
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Journal articleGuvenel AK, Chiu C, Openshaw PJM, 2014,
Current concepts and progress in RSV vaccine development
, EXPERT REVIEW OF VACCINES, Vol: 13, Pages: 333-344, ISSN: 1476-0584- Author Web Link
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- Citations: 42
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Journal articleBeverley PCL, Sridhar S, Lalvani A, et al., 2014,
Harnessing local and systemic immunity for vaccines against tuberculosis
, MUCOSAL IMMUNOLOGY, Vol: 7, Pages: 20-26, ISSN: 1933-0219- Author Web Link
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- Citations: 59
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