Journal article

Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice

  • Hauber, Ilona Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany
  • Hofmann-Sieber, Helga Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany
  • Chemnitz, Jan Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany
  • Dubrau, Danilo Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany
  • Chusainow, Janet Department of Medical Systems Biology, University Hospital and Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
  • Stucka, Rolf Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University Munich, Munich, Germany
  • 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
  • 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
  • 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
  • Hackmann, Karl Institute for Clinical Genetics, University Hospital and Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
  • Schröck, Evelin Institute for Clinical Genetics, University Hospital and Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
  • Schumacher, Udo Institute for Anatomy and Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Lindner, Christoph Department of Gynecology, Day Kimball Healthcare Hospital, Hamburg, Germany
  • Grundhoff, Adam Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany
  • Baum, Christopher Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany
  • 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
  • Buchholz, Frank Department of Medical Systems Biology, University Hospital and Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
  • Hauber, Joachim Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Germany
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    26.09.2013
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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  • English
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Medicine
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https://susi.usi.ch/usi/documents/318975
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