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

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Title: Highly Significant Antiviral Activity of HIV-1 LTR-Specific Tre-Recombinase in Humanized Mice
Author: 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

Note: Order does not necessarily reflect citation order of authors.

Citation: Hauber, I., H. Hofmann-Sieber, J. Chemnitz, D. Dubrau, J. Chusainow, R. Stucka, P. Hartjen, et al. 2013. “Highly Significant Antiviral Activity of HIV-1 LTR-Specific Tre-Recombinase in Humanized Mice.” PLoS Pathogens 9 (9): e1003587. doi:10.1371/journal.ppat.1003587. http://dx.doi.org/10.1371/journal.ppat.1003587.
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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.
Published Version: doi:10.1371/journal.ppat.1003587
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784474/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11878944
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