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

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Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice. / Hauber, Ilona; Hofmann-Sieber, Helga; Chemnitz, Jan; Dubrau, Danilo; Chusainow, Janet; Stucka, Rolf; Hartjen, Philip; Schambach, Axel; Ziegler, Patrick; Hackmann, Karl; Schröck, Evelin; Schumacher, Udo; Lindner, Christoph; Grundhoff, Adam; Baum, Christopher; Manz, Markus G; Buchholz, Frank; Hauber, Joachim.

in: PLOS PATHOG, Jahrgang 9, Nr. 9, 01.01.2013, S. e1003587.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

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, MG, Buchholz, F & Hauber, J 2013, 'Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice', PLOS PATHOG, Jg. 9, Nr. 9, S. e1003587. https://doi.org/10.1371/journal.ppat.1003587

APA

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. (2013). Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice. PLOS PATHOG, 9(9), e1003587. https://doi.org/10.1371/journal.ppat.1003587

Vancouver

Hauber I, Hofmann-Sieber H, Chemnitz J, Dubrau D, Chusainow J, Stucka R et al. Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice. PLOS PATHOG. 2013 Jan 1;9(9):e1003587. https://doi.org/10.1371/journal.ppat.1003587

Bibtex

@article{548af2423e6a49a7b9c54b6d7d39f3b9,
title = "Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice",
abstract = "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.",
keywords = "Animals, Genetic Therapy, Genetic Vectors, HIV Infections, HIV Long Terminal Repeat, HIV-1, Humans, Integrases, Mice, Mice, Knockout, Proviruses, Transduction, Genetic, Transplantation Chimera, Virus Integration",
author = "Ilona Hauber and Helga Hofmann-Sieber and Jan Chemnitz and Danilo Dubrau and Janet Chusainow and Rolf Stucka and Philip Hartjen and Axel Schambach and Patrick Ziegler and Karl Hackmann and Evelin Schr{\"o}ck and Udo Schumacher and Christoph Lindner and Adam Grundhoff and Christopher Baum and Manz, {Markus G} and Frank Buchholz and Joachim Hauber",
year = "2013",
month = jan,
day = "1",
doi = "10.1371/journal.ppat.1003587",
language = "English",
volume = "9",
pages = "e1003587",
journal = "PLOS PATHOG",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "9",

}

RIS

TY - JOUR

T1 - Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice

AU - Hauber, Ilona

AU - Hofmann-Sieber, Helga

AU - Chemnitz, Jan

AU - Dubrau, Danilo

AU - Chusainow, Janet

AU - Stucka, Rolf

AU - Hartjen, Philip

AU - Schambach, Axel

AU - Ziegler, Patrick

AU - Hackmann, Karl

AU - Schröck, Evelin

AU - Schumacher, Udo

AU - Lindner, Christoph

AU - Grundhoff, Adam

AU - Baum, Christopher

AU - Manz, Markus G

AU - Buchholz, Frank

AU - Hauber, Joachim

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

KW - Animals

KW - Genetic Therapy

KW - Genetic Vectors

KW - HIV Infections

KW - HIV Long Terminal Repeat

KW - HIV-1

KW - Humans

KW - Integrases

KW - Mice

KW - Mice, Knockout

KW - Proviruses

KW - Transduction, Genetic

KW - Transplantation Chimera

KW - Virus Integration

U2 - 10.1371/journal.ppat.1003587

DO - 10.1371/journal.ppat.1003587

M3 - SCORING: Journal article

C2 - 24086129

VL - 9

SP - e1003587

JO - PLOS PATHOG

JF - PLOS PATHOG

SN - 1553-7366

IS - 9

ER -