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  • 1
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    A genetically humanized mouse model for hepatitis C virus infection (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-06-10
    Description: Hepatitis C virus (HCV) remains a major medical problem. Antiviral treatment is only partially effective and a vaccine does not exist. Development of more effective therapies has been hampered by the lack of a suitable small animal model. Although xenotransplantation of immunodeficient mice with human hepatocytes has shown promise, these models are subject to important challenges. Building on the previous observation that CD81 and occludin comprise the minimal human factors required to render mouse cells permissive to HCV entry in vitro, we attempted murine humanization via a genetic approach. Here we show that expression of two human genes is sufficient to allow HCV infection of fully immunocompetent inbred mice. We establish a precedent for applying mouse genetics to dissect viral entry and validate the role of scavenger receptor type B class I for HCV uptake. We demonstrate that HCV can be blocked by passive immunization, as well as showing that a recombinant vaccinia virus vector induces humoral immunity and confers partial protection against heterologous challenge. This system recapitulates a portion of the HCV life cycle in an immunocompetent rodent for the first time, opening opportunities for studying viral pathogenesis and immunity and comprising an effective platform for testing HCV entry inhibitors in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159410/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159410/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dorner, Marcus -- Horwitz, Joshua A -- Robbins, Justin B -- Barry, Walter T -- Feng, Qian -- Mu, Kathy -- Jones, Christopher T -- Schoggins, John W -- Catanese, Maria Teresa -- Burton, Dennis R -- Law, Mansun -- Rice, Charles M -- Ploss, Alexander -- F32DK081193/DK/NIDDK NIH HHS/ -- F32DK082155/DK/NIDDK NIH HHS/ -- R01 AI071084/AI/NIAID NIH HHS/ -- R01 AI071084-04/AI/NIAID NIH HHS/ -- R01 AI072613/AI/NIAID NIH HHS/ -- R01 AI072613-05/AI/NIAID NIH HHS/ -- R01 AI079031/AI/NIAID NIH HHS/ -- R01 AI079031-04/AI/NIAID NIH HHS/ -- R01 DK085713/DK/NIDDK NIH HHS/ -- R01 DK085713-03/DK/NIDDK NIH HHS/ -- R01AI071084/AI/NIAID NIH HHS/ -- R01AI072613/AI/NIAID NIH HHS/ -- R01AI079031/AI/NIAID NIH HHS/ -- RC1 DK087193/DK/NIDDK NIH HHS/ -- RC1 DK087193-02/DK/NIDDK NIH HHS/ -- RC1DK087193/DK/NIDDK NIH HHS/ -- England -- Nature. 2011 Jun 8;474(7350):208-11. doi: 10.1038/nature10168.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for the Study of Hepatitis C, The Rockefeller University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21654804" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoviridae/genetics/physiology ; Animals ; Antibodies, Blocking/immunology ; Antigens, CD/genetics/metabolism ; Antigens, CD81 ; Cells, Cultured ; Claudin-1 ; *Disease Models, Animal ; Genotype ; Hepacivirus/genetics/metabolism/*physiology ; Hepatitis C/*genetics/*virology ; Hepatocytes/cytology/*metabolism/*virology ; Humans ; Immunization, Passive ; Membrane Proteins/genetics/metabolism ; Mice ; Receptors, Virus/genetics/metabolism ; Scavenger Receptors, Class B/genetics/metabolism ; Transfection ; Viral Tropism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Completion of the entire hepatitis C virus life cycle in genetically humanized mice (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-08-02
    Description: More than 130 million people worldwide chronically infected with hepatitis C virus (HCV) are at risk of developing severe liver disease. Antiviral treatments are only partially effective against HCV infection, and a vaccine is not available. Development of more efficient therapies has been hampered by the lack of a small animal model. Building on the observation that CD81 and occludin (OCLN) comprise the minimal set of human factors required to render mouse cells permissive to HCV entry, we previously showed that transient expression of these two human genes is sufficient to allow viral uptake into fully immunocompetent inbred mice. Here we demonstrate that transgenic mice stably expressing human CD81 and OCLN also support HCV entry, but innate and adaptive immune responses restrict HCV infection in vivo. Blunting antiviral immunity in genetically humanized mice infected with HCV results in measurable viraemia over several weeks. In mice lacking the essential cellular co-factor cyclophilin A (CypA), HCV RNA replication is markedly diminished, providing genetic evidence that this process is faithfully recapitulated. Using a cell-based fluorescent reporter activated by the NS3-4A protease we visualize HCV infection in single hepatocytes in vivo. Persistently infected mice produce de novo infectious particles, which can be inhibited with directly acting antiviral drug treatment, thereby providing evidence for the completion of the entire HCV life cycle in inbred mice. This genetically humanized mouse model opens new opportunities to dissect genetically HCV infection in vivo and provides an important preclinical platform for testing and prioritizing drug candidates and may also have utility for evaluating vaccine efficacy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858853/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858853/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dorner, Marcus -- Horwitz, Joshua A -- Donovan, Bridget M -- Labitt, Rachael N -- Budell, William C -- Friling, Tamar -- Vogt, Alexander -- Catanese, Maria Teresa -- Satoh, Takashi -- Kawai, Taro -- Akira, Shizuo -- Law, Mansun -- Rice, Charles M -- Ploss, Alexander -- R01 AI072613/AI/NIAID NIH HHS/ -- R01 AI079031/AI/NIAID NIH HHS/ -- R01 AI099284/AI/NIAID NIH HHS/ -- R01 AI107301/AI/NIAID NIH HHS/ -- R01 CA057973/CA/NCI NIH HHS/ -- R01AI072613/AI/NIAID NIH HHS/ -- R01AI079031/AI/NIAID NIH HHS/ -- R01AI099284/AI/NIAID NIH HHS/ -- R01CA057973/CA/NCI NIH HHS/ -- RC1 DK087193/DK/NIDDK NIH HHS/ -- RC1DK087193/DK/NIDDK NIH HHS/ -- England -- Nature. 2013 Sep 12;501(7466):237-41. doi: 10.1038/nature12427. Epub 2013 Jul 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for the Study of Hepatitis C, The Rockefeller University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23903655" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD81/genetics/metabolism ; Cell Line ; Cyclophilin A/genetics/metabolism ; *Disease Models, Animal ; *Genetic Engineering ; Hepacivirus/immunology/*physiology ; Hepatitis C/*genetics/immunology/*virology ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Occludin/genetics/metabolism ; STAT1 Transcription Factor/deficiency ; Viremia/virology ; Virion/growth & development/physiology ; *Virus Replication
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    HIV therapy by a combination of broadly neutralizing antibodies in humanized mice (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-10-30
    Description: Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy, the longer half-life of antibodies led to control of viraemia for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809838/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809838/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klein, Florian -- Halper-Stromberg, Ariel -- Horwitz, Joshua A -- Gruell, Henning -- Scheid, Johannes F -- Bournazos, Stylianos -- Mouquet, Hugo -- Spatz, Linda A -- Diskin, Ron -- Abadir, Alexander -- Zang, Trinity -- Dorner, Marcus -- Billerbeck, Eva -- Labitt, Rachael N -- Gaebler, Christian -- Marcovecchio, Paola M -- Incesu, Reha-Baris -- Eisenreich, Thomas R -- Bieniasz, Paul D -- Seaman, Michael S -- Bjorkman, Pamela J -- Ravetch, Jeffrey V -- Ploss, Alexander -- Nussenzweig, Michel C -- 1UM1AI100663/AI/NIAID NIH HHS/ -- AI081677/AI/NIAID NIH HHS/ -- P01 AI081677/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Dec 6;492(7427):118-22. doi: 10.1038/nature11604. Epub 2012 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23103874" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/immunology/therapeutic use ; Antibodies, Neutralizing/*immunology/*therapeutic use ; Antibody Specificity/immunology ; Disease Models, Animal ; HIV Antibodies/*immunology/*therapeutic use ; HIV Infections/*drug therapy/*immunology/virology ; HIV-1/genetics/growth & development/immunology/isolation & purification ; Half-Life ; Humans ; Immunization, Passive ; Mice ; Mice, Inbred NOD ; Time Factors ; Viral Load/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection (2018)
    Springer Nature
    Details
    Publication Date: 2018-02-15
    Description: 3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection 3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection, Published online: 14 February 2018; doi:10.1038/s41467-018-02969-8 Long-term in vitro models for hepatitis B virus (HBV) infection are important to understand this infection, but are lacking. Here the authors develop a microfluidic primary human hepatocyte organoid culture system that can be maintained over 40 days and recapitulates all of the steps of the HBV life cycle.
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 5
    Electronic Resource
    Electronic Resource
    Oxidative phosphorylation and some related phenomena in pigment granules of mouse melanomas
    Amsterdam : Elsevier
    BBA - Biochimica et Biophysica Acta 48 (1961), S. 534-546 
    Details
    ISSN: 0006-3002
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0006-3002(61)90051-8
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    Paper (German National Licenses)
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  • 6
    Electronic Resource
    Electronic Resource
    Studies on structure-function relationships of human choriogonadotropins with C-terminally shortened α-subunits. I. Receptor binding and immunologic properties
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Molecular Cell Research 844 (1985), S. 62-66 
    Details
    ISSN: 0167-4889
    Keywords: Choriogonadotropin ; Immunological properties ; Receptor binding
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0167-4889(85)90234-4
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  • 7
    Electronic Resource
    Electronic Resource
    On the ^1H-NMR spectra of highly charged multi-triphenylmethylium ions
    Amsterdam : Elsevier
    Tetrahedron Letters 29 (1988), S. 5501-5504 
    Details
    ISSN: 0040-4039
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/S0040-4039(00)80797-2
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  • 8
    Electronic Resource
    Electronic Resource
    Purification and characterization of human chorionic gonadotropin
    Amsterdam : Elsevier
    FEBS Letters 15 (1971), S. 33-35 
    Details
    ISSN: 0014-5793
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0014-5793(71)80073-X
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  • 9
    Electronic Resource
    Electronic Resource
    Chemical modification of human chorionic gonadotropin and its biological and immunological characterization
    Amsterdam : Elsevier
    FEBS Letters 15 (1971), S. 36-39 
    Details
    ISSN: 0014-5793
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0014-5793(71)80074-1
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  • 10
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    Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-08-20
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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