Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice
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Hauber, Ilona
Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany
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Hofmann-Sieber, Helga
Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany
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Chemnitz, Jan
Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany
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Dubrau, Danilo
Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany
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Chusainow, Janet
Department of Medical Systems Biology, University Hospital and Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
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Stucka, Rolf
Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Munich, Germany
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Hartjen, Philip
Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany - Infectious Diseases Unit, I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Schambach, Axel
Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany - Division of Hematology/Oncology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America
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Ziegler, Patrick
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Klinik für Onkologie, Hämatologie und Stammzelltransplantation, RWTH Aachen University, Aachen, Germany
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Hackmann, Karl
Institute for Clinical Genetics, University Hospital and Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
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Schröck, Evelin
Institute for Clinical Genetics, University Hospital and Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
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Schumacher, Udo
Institute for Anatomy and Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Lindner, Christoph
Department of Gynecology, Day Kimball Healthcare Hospital, Hamburg, Germany
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Grundhoff, Adam
Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany
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Baum, Christopher
Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany
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Manz, Markus G.
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - University Hospital Zürich, Division of Hematology, Zürich, Switzerland
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Buchholz, Frank
Department of Medical Systems Biology, University Hospital and Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
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Hauber, Joachim
Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany
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Published in:
- Plos pathogens. - 2013, vol. 9, no. 9, p. e1003587
English
Stable integration of HIV proviral DNA into host cell chromosomes, a hallmark and essential feature of the retroviral life cycle, establishes the infection permanently. Current antiretroviral combination drug therapy cannot cure HIV infection. However, expressing an engineered HIV-1 long terminal repeat (LTR) site-specific recombinase (Tre), shown to excise integrated proviral DNA in vitro, may provide a novel and highly promising antiviral strategy. We report here the conditional expression of Tre-recombinase from an advanced lentiviral self-inactivation (SIN) vector in HIV-infected cells. We demonstrate faithful transgene expression, resulting in accurate provirus excision in the absence of cytopathic effects. Moreover, pronounced Tre-mediated antiviral effects are demonstrated in vivo, particularly in humanized Rag2−/−γc−/− mice engrafted with either Tre-transduced primary CD4+ T cells, or Tre-transduced CD34+ hematopoietic stem and progenitor cells (HSC). Taken together, our data support the use of Tre-recombinase in novel therapy strategies aiming to provide a cure for HIV.
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https://n2t.net/ark:/12658/srd1318975
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