175 research outputs found

    Effectiveness of common household cleaning agents in reducing the viability of human influenza A/H1N1

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    In the event of an influenza pandemic, the majority of people infected will be nursed at home. It is therefore important to determine simple methods for limiting the spread of the virus within the home. The purpose of this work was to test a representative range of common household cleaning agents for their effectiveness at killing or reducing the viability of influenza A virus

    The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NFκB-dependent promoter antagonism in chicken cells.

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    The accessory protein, PB1-F2, of influenza A virus (IAV) functions in a chicken host to prolong infectious virus shedding and thus the transmission window. Here we show that this delay in virus clearance by PB1-F2 in chickens is accompanied by reduced transcript levels of type 1 interferon (IFN)-induced genes and NFκB-activated pro-inflammation cytokines. In vitro, two avian influenza isolate-derived PB1-F2 proteins, H9N2 UDL01 and H5N1 5092, exhibited the same antagonism of the IFN and pro-inflammation induction pathways seen in vivo, but to different extents. The two PB1-F2 proteins had different cellular localization in chicken cells, with H5N1 5092 being predominantly mitochondrial-associated and H9N2 UDL being cytoplasmic but not mitochondrial-localized. We hypothesized that PB1-F2 localization might influence the functionality of the protein during infection and that the protein sequence could alter cellular localization. We demonstrated that the sequence of the C-terminus of PB1-F2 determined cytoplasmic localization in chicken cells and this was linked with protein instability. Mitochondrial localization of PB1-F2 resulted in reduced antagonism of an NFκB-dependent promoter. In parallel, mitochondrial localization of PB1-F2 increased the potency of chicken IFN 2 induction antagonism. We suggest that mitochondrial localization of PB1-F2 restricts interaction with cytoplasmic-located IKKβ, reducing NFκB-responsive promoter antagonism, but enhances antagonism of the IFN2 promoter through interaction with the mitochondrial adaptor MAVS. Our study highlights the differential mechanisms by which IAV PB1-F2 protein can dampen the avian host innate signalling response

    Anthropologie des relations hommes-animaux

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    Jean-Pierre Digard, directeur de recherche au CNRSNoëlie Vialles, maître de conférences au Collège de France avec la participation d’Arouna P. Ouédraogo, chargé de recherche à l’INRA Prenant appui sur ce constat élémentaire qu’il n’existe pas de société humaine sans animaux, et ainsi que les relations entre hommes et animaux sont constitutives de toute société humaine, le séminaire s’est proposé de traiter ces relations comme un objet anthropologique de plein droit, dont il est possible de me..

    Anthropologie des relations hommes-animaux

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    Mercredi 5 novembre 2003 Jean-Pierre Digard, Comment concevoir une anthropologie de la domestication animale ? Mercredi 19 novembre 2003 Jean-Pierre Digard, La notion de système domesticatoire Mercredi 3 décembre 2003 Frédéric Saumade, Le système domesticatoire mexicain Mercredi 17 décembre 2003 Sarah Cabalion, Le système domesticatoire touareg Mercredi 7 janvier 2004 Michel Cartier, Le système domesticatoire chinois Mercredi 21 janvier 2004 Dominique Lestel, La sociabilité..

    The influence of viral coding sequences on pestivirus IRES activity reveals further parallels with translation initiation in prokaryotes

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    Classical swine fever virus (CSFV) is a member of the pestivirus family, which shares many features in common with hepatitis C virus (HCV). It is shown here that CSFV has an exceptionally efficient cis-acting internal ribosome entry segment (IRES), which, like that of HCV, is strongly influenced by the sequences immediately downstream of the initiation codon, and is optimal with viral coding sequences in this position. Constructs that retained 17 or more codons of viral coding sequence exhibited full IRES activity, but with only 12 codons, activity was approximately 66% of maximum in vitro (though close to maximum in transfected BHK cells), whereas with just 3 codons or fewer, the activity was only approximately 15% of maximum. The minimal coding region elements required for high activity were exchanged between HCV and CSFV. Although maximum activity was observed in each case with the homologous combination of coding region and 5' UTR, the heterologous combinations were sufficiently active to rule out a highly specific functional interplay between the 5' UTR and coding sequences. On the other hand, inversion of the coding sequences resulted in low IRES activity, particularly with the HCV coding sequences. RNA structure probing showed that the efficiency of internal initiation of these chimeric constructs correlated most closely with the degree of single-strandedness of the region around and immediately downstream of the initiation codon. The low activity IRESs could not be rescued by addition of supplementary eIF4A (the initiation factor with ATP-dependent RNA helicase activity). The extreme sensitivity to secondary structure around the initiation codon is likely to be due to the fact that the eIF4F complex (which has eIF4A as one of its subunits) is not required for and does not participate in initiation on these IRESs

    Ribosomal frameshifting used in influenza A virus expression occurs within the sequence UCC_UUU_CGU and is in the +1 direction

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    Programmed ribosomal frameshifting is used in the expression of many virus genes and some cellular genes. In eukaryotic systems, the most well-characterized mechanism involves –1 tandem tRNA slippage on an X_XXY_YYZ motif. By contrast, the mechanisms involved in programmed +1 (or −2) slippage are more varied and often poorly characterized. Recently, a novel gene, PA-X, was discovered in influenza A virus and found to be expressed via a shift to the +1 reading frame. Here, we identify, by mass spectrometric analysis, both the site (UCC_UUU_CGU) and direction (+1) of the frameshifting that is involved in PA-X expression. Related sites are identified in other virus genes that have previously been proposed to be expressed via +1 frameshifting. As these viruses infect insects (chronic bee paralysis virus), plants (fijiviruses and amalgamaviruses) and vertebrates (influenza A virus), such motifs may form a new class of +1 frameshift-inducing sequences that are active in diverse eukaryotes

    Constitutive TRIM22 expression within the respiratory tract identifies tissue-specific and cell-type dependent intrinsic immune barriers to influenza A virus infection

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    We hypothesized that increased expression of antiviral host factors at portals of viral entry may protect exposed tissues from the constant threat of invading pathogens. Comparative transcriptomic analysis identified the broad-acting restriction factor TRIM22 (TRIpartite Motif 22) to be among the most abundantly expressed antiviral host factors in the lung, a major portal of entry for many respiratory pathogens. This was surprising, as TRIM22 is currently considered to be an interferon stimulated gene (ISG) product that confers protection following the activation of pathogen-induced cytokine-mediated innate immune defences. Using human respiratory cell lines and the airways of rhesus macaques, we experimentally confirmed high levels of constitutive TRIM22 expression in the lung. In contrast, TRIM22 expression in many widely used transformed cell lines could only be observed following immune stimulation. Endogenous levels of TRIM22 in non-transformed cells were sufficient to restrict human and avian influenza A virus (IAV) infection by inhibiting the onset of viral transcription independently of cytokine-mediated innate immune defences. Thus, TRIM22 confers a pre-existing (intrinsic) tissue-specific immune barrier to IAV infection in the respiratory tract. We investigated whether the constitutive expression of TRIM22 was a characteristic shared by other ISGs in human lung tissue. Transcriptomic analysis identified a large group of ISGs and IAV immuno-regulatory host factors that were similarly enriched in the lung relative to other mucosal tissues, but whose expression was downregulated in transformed cell-lines. We identify common networks of immune gene downregulation which correlated with enhanced permissivity of transformed cells to initiate IAV replication. Our data highlight the importance of tissue-specific and cell-type dependent patterns of pre-existing immune gene expression in the intrinsic intracellular restriction of IAV; findings highly relevant to the immune regulation of many clinically important respiratory pathogens

    "We're all the same here"—Investigating the rehabilitative climate of a re-rolled sexual offender prison: a qualitative longitudinal study

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    Understanding how individuals with sexual convictions experience prison and its environment is important because such experiences can impact on rehabilitation outcomes. This is the first qualitative longitudinal investigation that explores the experiences of prisoners in a prison exclusively for individuals with sexual convictions over time. The purpose of this research was to explore the rehabilitative and therapeutic climate of a recently re-rolled prison (a general prison turned into a prison only for individuals who have sexually offended) at two time points (T1 at reroll and T2 a year later). The study focuses on prisoners perspectives of the purpose of the prison, experience of prison life, relationships in the prison, and the prison regime over time. Twenty interviews were conducted across the time points and revealed two main superordinate themes “‘Being’ in a prison for individuals with sexual convictions” and “obstructions to change". This research adds to the emerging body of knowledge surrounding the importance of the wider prison environment on the rehabilitation of individuals with sexual convictions and on the benefits and risks of co-locating men who have committed sexual offences in the same prison site. It also has implications wider than rehabilitation of those convicted of sexual offences and has insights for the types of environment and prisoner-staff relationships that are conducive to rehabilitation
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