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  1. Article ; Online: Ferret Interferon (IFN)-Inducible Transmembrane Proteins Are Upregulated by both IFN-α and Influenza Virus Infection.

    Horman, William S J / Kedzierska, Katherine / Rootes, Christina L / Bean, Andrew G D / Nguyen, Thi H O / Layton, Daniel S

    Journal of virology

    2021  Volume 95, Issue 14, Page(s) e0011121

    Abstract: The current fears of a future influenza pandemic have resulted in an increased emphasis on the development and testing of novel therapeutic strategies against the virus. Fundamental to this is the ferret model of influenza infection, which is critical in ...

    Abstract The current fears of a future influenza pandemic have resulted in an increased emphasis on the development and testing of novel therapeutic strategies against the virus. Fundamental to this is the ferret model of influenza infection, which is critical in examining pathogenesis and treatment. Nevertheless, a precise evaluation of the efficacy of any treatment strategy in ferrets is reliant on understanding the immune response in this model. Interferon-inducible transmembrane proteins (IFITMs) are interferon-stimulated proteins shown to be critically important in the host immune response against viral infections. These proteins confer intrinsic innate immunity to pH-dependent viruses such as influenza viruses and can inhibit cytosolic entry of such viruses to limit the severity of infection following interferon upregulation. Mutations in IFITM genes in humans have been identified as key risk factors for worsened disease progression, particularly in the case of avian influenza viruses such as H7N9. While the IFITM genes of humans and mice have been well characterized, no studies have been conducted to classify the IFITM locus and interferon-driven upregulation of IFITMs in ferrets. Here, we show the architecture of the ferret IFITM locus and its synteny to the IFITM locus of other mammalian and avian species. Furthermore, we show that ferret
    MeSH term(s) Animals ; Cell Line ; Conserved Sequence ; Disease Models, Animal ; Ferrets/immunology ; Ferrets/metabolism ; Ferrets/virology ; Humans ; Influenza A Virus, H1N1 Subtype ; Interferon-alpha/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Models, Molecular ; Orthomyxoviridae Infections/genetics ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/metabolism ; Polymerase Chain Reaction ; Sequence Analysis, Protein ; Up-Regulation
    Chemical Substances Interferon-alpha ; Membrane Proteins
    Language English
    Publishing date 2021-06-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.00111-21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Drivers of Pathology in Zoonotic Avian Influenza: The Interplay Between Host and Pathogen.

    Horman, William S J / Nguyen, Thi H O / Kedzierska, Katherine / Bean, Andrew G D / Layton, Daniel S

    Frontiers in immunology

    2018  Volume 9, Page(s) 1812

    Abstract: The emergence of zoonotic strains of avian influenza (AI) that cause high rates of mortality in people has caused significant global concern, with a looming threat that one of these strains may develop sustained human-to-human transmission and cause a ... ...

    Abstract The emergence of zoonotic strains of avian influenza (AI) that cause high rates of mortality in people has caused significant global concern, with a looming threat that one of these strains may develop sustained human-to-human transmission and cause a pandemic outbreak. Most notable of these viral strains are the H5N1 highly pathogenic AI and the H7N9 low pathogenicity AI viruses, both of which have mortality rates above 30%. Understanding of their mechanisms of infection and pathobiology is key to our preparation for these and future viral strains of high consequence. AI viruses typically circulate in wild bird populations, commonly infecting waterfowl and also regularly entering commercial poultry flocks. Live poultry markets provide an ideal environment for the spread AI and potentially the selection of mutants with a greater propensity for infecting humans because of the potential for spill over from birds to humans. Pathology from these AI virus infections is associated with a dysregulated immune response, which is characterized by systemic spread of the virus, lymphopenia, and hypercytokinemia. It has been well documented that host/pathogen interactions, particularly molecules of the immune system, play a significant role in both disease susceptibility as well as disease outcome. Here, we review the immune/virus interactions in both avian and mammalian species, and provide an overview or our understanding of how immune dysregulation is driven. Understanding these susceptibility factors is critical for the development of new vaccines and therapeutics to combat the next pandemic influenza.
    MeSH term(s) Animals ; Birds ; Communicable Diseases, Emerging ; Disease Outbreaks ; Disease Susceptibility ; Genetic Fitness ; Host-Pathogen Interactions ; Humans ; Influenza A virus/classification ; Influenza A virus/physiology ; Influenza in Birds/epidemiology ; Influenza in Birds/virology ; Influenza, Human/diagnosis ; Influenza, Human/epidemiology ; Influenza, Human/transmission ; Influenza, Human/virology ; Species Specificity ; Zoonoses
    Language English
    Publishing date 2018-08-08
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2018.01812
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Dynamics of the Ferret Immune Response During H7N9 Influenza Virus Infection.

    Horman, William S J / Nguyen, Thi H O / Kedzierska, Katherine / Butler, Jeffrey / Shan, Songhua / Layton, Rachel / Bingham, John / Payne, Jean / Bean, Andrew G D / Layton, Daniel S

    Frontiers in immunology

    2020  Volume 11, Page(s) 559113

    Abstract: As the recent outbreak of SARS-CoV-2 has highlighted, the threat of a pandemic event from zoonotic viruses, such as the deadly influenza A/H7N9 virus subtype, continues to be a major global health concern. H7N9 virus strains appear to exhibit greater ... ...

    Abstract As the recent outbreak of SARS-CoV-2 has highlighted, the threat of a pandemic event from zoonotic viruses, such as the deadly influenza A/H7N9 virus subtype, continues to be a major global health concern. H7N9 virus strains appear to exhibit greater disease severity in mammalian hosts compared to natural avian hosts, though the exact mechanisms underlying this are somewhat unclear. Knowledge of the H7N9 host-pathogen interactions have mainly been constrained to natural sporadic human infections. To elucidate the cellular immune mechanisms associated with disease severity and progression, we used a ferret model to closely resemble disease outcomes in humans following influenza virus infection. Intriguingly, we observed variable disease outcomes when ferrets were inoculated with the A/Anhui/1/2013 (H7N9) strain. We observed relatively reduced antigen-presenting cell activation in lymphoid tissues which may be correlative with increased disease severity. Additionally, depletions in CD8
    MeSH term(s) Animals ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/pathology ; Betacoronavirus/immunology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; COVID-19 ; Coronavirus Infections/immunology ; Disease Models, Animal ; Ferrets ; Host-Pathogen Interactions/immunology ; Humans ; Influenza A Virus, H7N9 Subtype/physiology ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/pathology ; Pandemics ; Pneumonia, Viral/immunology ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-09-24
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.559113
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Audio / Video ; Online: Image_1_The Dynamics of the Ferret Immune Response During H7N9 Influenza Virus Infection.TIF

    William S. J. Horman / Thi H. O. Nguyen / Katherine Kedzierska / Jeffrey Butler / Songhua Shan / Rachel Layton / John Bingham / Jean Payne / Andrew G. D. Bean / Daniel S. Layton

    2020  

    Abstract: As the recent outbreak of SARS-CoV-2 has highlighted, the threat of a pandemic event from zoonotic viruses, such as the deadly influenza A/H7N9 virus subtype, continues to be a major global health concern. H7N9 virus strains appear to exhibit greater ... ...

    Abstract As the recent outbreak of SARS-CoV-2 has highlighted, the threat of a pandemic event from zoonotic viruses, such as the deadly influenza A/H7N9 virus subtype, continues to be a major global health concern. H7N9 virus strains appear to exhibit greater disease severity in mammalian hosts compared to natural avian hosts, though the exact mechanisms underlying this are somewhat unclear. Knowledge of the H7N9 host-pathogen interactions have mainly been constrained to natural sporadic human infections. To elucidate the cellular immune mechanisms associated with disease severity and progression, we used a ferret model to closely resemble disease outcomes in humans following influenza virus infection. Intriguingly, we observed variable disease outcomes when ferrets were inoculated with the A/Anhui/1/2013 (H7N9) strain. We observed relatively reduced antigen-presenting cell activation in lymphoid tissues which may be correlative with increased disease severity. Additionally, depletions in CD8 + T cells were not apparent in sick animals. This study provides further insight into the ways that lymphocytes maturate and traffic in response to H7N9 infection in the ferret model.
    Keywords Immunology ; Applied Immunology (incl. Antibody Engineering ; Xenotransplantation and T-cell Therapies) ; Autoimmunity ; Cellular Immunology ; Humoural Immunology and Immunochemistry ; Immunogenetics (incl. Genetic Immunology) ; Innate Immunity ; Transplantation Immunology ; Tumour Immunology ; Immunology not elsewhere classified ; Genetic Immunology ; Animal Immunology ; Veterinary Immunology ; influenza ; H7N9 ; ferrets ; antigen presenting cells ; animal model ; zoonoses ; covid19
    Subject code 570
    Publishing date 2020-09-24T04:31:12Z
    Publishing country uk
    Document type Audio / Video ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: The Dynamics of the Ferret Immune Response During H7N9 Influenza Virus Infection

    William S. J. Horman / Thi H. O. Nguyen / Katherine Kedzierska / Jeffrey Butler / Songhua Shan / Rachel Layton / John Bingham / Jean Payne / Andrew G. D. Bean / Daniel S. Layton

    Frontiers in Immunology, Vol

    2020  Volume 11

    Abstract: As the recent outbreak of SARS-CoV-2 has highlighted, the threat of a pandemic event from zoonotic viruses, such as the deadly influenza A/H7N9 virus subtype, continues to be a major global health concern. H7N9 virus strains appear to exhibit greater ... ...

    Abstract As the recent outbreak of SARS-CoV-2 has highlighted, the threat of a pandemic event from zoonotic viruses, such as the deadly influenza A/H7N9 virus subtype, continues to be a major global health concern. H7N9 virus strains appear to exhibit greater disease severity in mammalian hosts compared to natural avian hosts, though the exact mechanisms underlying this are somewhat unclear. Knowledge of the H7N9 host-pathogen interactions have mainly been constrained to natural sporadic human infections. To elucidate the cellular immune mechanisms associated with disease severity and progression, we used a ferret model to closely resemble disease outcomes in humans following influenza virus infection. Intriguingly, we observed variable disease outcomes when ferrets were inoculated with the A/Anhui/1/2013 (H7N9) strain. We observed relatively reduced antigen-presenting cell activation in lymphoid tissues which may be correlative with increased disease severity. Additionally, depletions in CD8+ T cells were not apparent in sick animals. This study provides further insight into the ways that lymphocytes maturate and traffic in response to H7N9 infection in the ferret model.
    Keywords influenza ; H7N9 ; ferrets ; antigen presenting cells ; animal model ; zoonoses ; Immunologic diseases. Allergy ; RC581-607 ; covid19
    Subject code 570
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: The Dynamics of the Ferret Immune Response During H7N9 Influenza Virus Infection

    Horman, William S J / Nguyen, Thi H O / Kedzierska, Katherine / Butler, Jeffrey / Shan, Songhua / Layton, Rachel / Bingham, John / Payne, Jean / Bean, Andrew G D / Layton, Daniel S

    Front Immunol

    Abstract: As the recent outbreak of SARS-CoV-2 has highlighted, the threat of a pandemic event from zoonotic viruses, such as the deadly influenza A/H7N9 virus subtype, continues to be a major global health concern. H7N9 virus strains appear to exhibit greater ... ...

    Abstract As the recent outbreak of SARS-CoV-2 has highlighted, the threat of a pandemic event from zoonotic viruses, such as the deadly influenza A/H7N9 virus subtype, continues to be a major global health concern. H7N9 virus strains appear to exhibit greater disease severity in mammalian hosts compared to natural avian hosts, though the exact mechanisms underlying this are somewhat unclear. Knowledge of the H7N9 host-pathogen interactions have mainly been constrained to natural sporadic human infections. To elucidate the cellular immune mechanisms associated with disease severity and progression, we used a ferret model to closely resemble disease outcomes in humans following influenza virus infection. Intriguingly, we observed variable disease outcomes when ferrets were inoculated with the A/Anhui/1/2013 (H7N9) strain. We observed relatively reduced antigen-presenting cell activation in lymphoid tissues which may be correlative with increased disease severity. Additionally, depletions in CD8+ T cells were not apparent in sick animals. This study provides further insight into the ways that lymphocytes maturate and traffic in response to H7N9 infection in the ferret model.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #868963
    Database COVID19

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  7. Article ; Online: ChAdOx1 nCoV-19 (AZD1222) vaccine candidate significantly reduces SARS-CoV-2 shedding in ferrets.

    Marsh, Glenn A / McAuley, Alexander J / Au, Gough G / Riddell, Sarah / Layton, Daniel / Singanallur, Nagendrakumar B / Layton, Rachel / Payne, Jean / Durr, Peter A / Bender, Hannah / Barr, Jennifer A / Bingham, John / Boyd, Victoria / Brown, Sheree / Bruce, Matthew P / Burkett, Kathie / Eastwood, Teresa / Edwards, Sarah / Gough, Tamara /
    Halpin, Kim / Harper, Jenni / Holmes, Clare / Horman, William S J / van Vuren, Petrus Jansen / Lowther, Suzanne / Maynard, Kate / McAuley, Kristen D / Neave, Matthew J / Poole, Timothy / Rootes, Christina / Rowe, Brenton / Soldani, Elisha / Stevens, Vittoria / Stewart, Cameron R / Suen, Willy W / Tachedjian, Mary / Todd, Shawn / Trinidad, Lee / Walter, Duane / Watson, Naomi / Drew, Trevor W / Gilbert, Sarah C / Lambe, Teresa / Vasan, S S

    NPJ vaccines

    2021  Volume 6, Issue 1, Page(s) 67

    Abstract: Vaccines against SARS-CoV-2 are likely to be critical in the management of the ongoing pandemic. A number of candidates are in Phase III human clinical trials, including ChAdOx1 nCoV-19 (AZD1222), a replication-deficient chimpanzee adenovirus-vectored ... ...

    Abstract Vaccines against SARS-CoV-2 are likely to be critical in the management of the ongoing pandemic. A number of candidates are in Phase III human clinical trials, including ChAdOx1 nCoV-19 (AZD1222), a replication-deficient chimpanzee adenovirus-vectored vaccine candidate. In preclinical trials, the efficacy of ChAdOx1 nCoV-19 against SARS-CoV-2 challenge was evaluated in a ferret model of infection. Groups of ferrets received either prime-only or prime-boost administration of ChAdOx1 nCoV-19 via the intramuscular or intranasal route. All ChAdOx1 nCoV-19 administration combinations resulted in significant reductions in viral loads in nasal-wash and oral swab samples. No vaccine-associated adverse events were observed associated with the ChAdOx1 nCoV-19 candidate, with the data from this study suggesting it could be an effective and safe vaccine against COVID-19. Our study also indicates the potential for intranasal administration as a way to further improve the efficacy of this leading vaccine candidate.
    Language English
    Publishing date 2021-05-10
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-021-00315-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Gfi1 integrates progenitor versus granulocytic transcriptional programming.

    Horman, Shane R / Velu, Chinavenmeni S / Chaubey, Aditya / Bourdeau, Tristan / Zhu, Jinfang / Paul, William E / Gebelein, Brian / Grimes, H Leighton

    Blood

    2009  Volume 113, Issue 22, Page(s) 5466–5475

    Abstract: In patients with severe congenital neutropenia (SCN) and mice with growth factor independent-1 (Gfi1) loss of function, arrested myeloid progenitors accumulate, whereas terminal granulopoiesis is blocked. One might assume that Gfi-null progenitors ... ...

    Abstract In patients with severe congenital neutropenia (SCN) and mice with growth factor independent-1 (Gfi1) loss of function, arrested myeloid progenitors accumulate, whereas terminal granulopoiesis is blocked. One might assume that Gfi-null progenitors accumulate because they lack the ability to differentiate. Instead, our data indicate that Gfi1 loss of function deregulates 2 separable transcriptional programs, one of which controls the accumulation and lineage specification of myeloid progenitors, but not terminal granulopoiesis. We demonstrate that Gfi1 directly represses HoxA9, Pbx1, and Meis1 during normal myelopoiesis. Gfi1-/- progenitors exhibit elevated levels of HoxA9, Pbx1 and Meis1, exaggerated HoxA9-Pbx1-Meis1 activity, and progenitor transformation in collaboration with oncogenic K-Ras. Limiting HoxA9 alleles corrects, in a dose-dependent manner, in vivo and in vitro phenotypes observed with loss of Gfi1 in myeloid progenitor cells but did not rescue Gfi1-/- blocked granulopoiesis. Thus, Gfi1 integrates 2 events during normal myeloid differentiation; the suppression of a HoxA9-Pbx1-Meis1 progenitor program and the induction of a granulopoietic transcription program.
    MeSH term(s) Animals ; Cell Differentiation/genetics ; Cells, Cultured ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/physiology ; Embryonic Development/genetics ; Gene Expression Regulation, Developmental ; Genetic Predisposition to Disease ; Granulocyte Precursor Cells/metabolism ; Granulocyte Precursor Cells/physiology ; Granulocytes/metabolism ; Granulocytes/physiology ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Leukemia/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Ecotropic Viral Integration Site 1 Protein ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Pre-B-Cell Leukemia Transcription Factor 1 ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription Factors/physiology ; Transcription, Genetic/physiology
    Chemical Substances DNA-Binding Proteins ; Gfi1 protein, mouse ; Homeodomain Proteins ; Meis1 protein, mouse ; Myeloid Ecotropic Viral Integration Site 1 Protein ; Neoplasm Proteins ; Pbx1 protein, mouse ; Pre-B-Cell Leukemia Transcription Factor 1 ; Transcription Factors ; homeobox protein HOXA9
    Language English
    Publishing date 2009-04-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2008-09-179747
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.140: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 364: Show issues

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