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Highly Significant Antiviral Activity of HIV-1 LTR-Specific Tre-Recombinase in Humanized Mice
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نویسنده
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hauber i. ,hofmann-sieber h. ,chemnitz j. ,dubrau d. ,chusainow j. ,stucka r. ,hartjen p. ,schambach a. ,ziegler p. ,hackmann k. ,schröck e. ,schumacher u. ,lindner c. ,grundhoff a. ,baum c. ,manz m.g. ,buchholz f. ,hauber j.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 9
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چکیده
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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. © 2013 hauber et al.
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آدرس
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heinrich pette institute - leibniz institute for experimental virology,hamburg, Germany, heinrich pette institute - leibniz institute for experimental virology,hamburg, Germany, heinrich pette institute - leibniz institute for experimental virology,hamburg, Germany, heinrich pette institute - leibniz institute for experimental virology,hamburg, Germany, department of medical systems biology,university hospital,technische universität dresden,dresden, Germany, friedrich-baur-institute,department of neurology,ludwig-maximilians-university munich,munich, Germany, 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, institute of experimental hematology,hannover medical school,hannover,germany,division of hematology/oncology,children's hospital boston,harvard medical school,boston,ma, United States, institute for research in biomedicine,bellinzona,switzerland,klinik für onkologie,hämatologie und stammzelltransplantation,rwth aachen university,aachen, Germany, institute for clinical genetics,university hospital,technische universität dresden,dresden, Germany, institute for clinical genetics,university hospital,technische universität dresden,dresden, Germany, institute for anatomy and experimental morphology,university cancer center hamburg,university medical center hamburg-eppendorf,hamburg, Germany, department of gynecology,day kimball healthcare hospital,hamburg, Germany, heinrich pette institute - leibniz institute for experimental virology,hamburg, Germany, institute of experimental hematology,hannover medical school,hannover, Germany, institute for research in biomedicine,bellinzona,switzerland,university and university hospital zürich,division of hematology,zürich, Switzerland, department of medical systems biology,university hospital,technische universität dresden,dresden, Germany, heinrich pette institute - leibniz institute for experimental virology,hamburg, Germany
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Authors
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