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

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 re...

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Autores principales: Ilona Hauber, Helga Hofmann-Sieber, Jan Chemnitz, Danilo Dubrau, Janet Chusainow, Rolf Stucka, Philip Hartjen, Axel Schambach, Patrick Ziegler, Karl Hackmann, Evelin Schröck, Udo Schumacher, Christoph Lindner, Adam Grundhoff, Christopher Baum, Markus G Manz, Frank Buchholz, Joachim Hauber
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/a30385a2f1f846a49457496bcee83427
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Sumario: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.