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Open Access

Next-generation LTR-specific Tre-recombinase targets a majority of HIV-1 isolates

  • Joachim Hauber1,
  • Janet Karpinski2,
  • Ilona Hauber1,
  • Jan Chemnitz1,
  • Helga Hofmann-Sieber1,
  • Claus-Henning Nagel1,
  • Niklas Beschorner1,
  • Carola Schäfer1 and
  • Frank Buchholz2
BMC Infectious Diseases201414(Suppl 2):O18

https://doi.org/10.1186/1471-2334-14-S2-O18

Published: 23 May 2014

Keywords

Antiviral ActivityLong Terminal RepeatHumanize MouseHuman Cell CultureBroad Clinical Application

Introduction

HIV-1 integrates into the host chromosome and persists as a provirus flanked by long terminal repeats (LTR). To date, treatment regimens primarily target the virus enzymes, virus attachment or virus-cell fusion, but not the integrated provirus. Thus, current antiretroviral therapies (i.e. cART) cannot eradicate HIV-1, a fact that highlights the urgency of pursuing new strategies to find a cure for HIV/AIDS.

Previously, we engineered an experimental LTR-specific recombinase (Tre-recombinase) that can effectively excise integrated HIV-1 proviral DNA from infected human cell cultures (Sarkar et al. 2007 Science 316:1912). Subsequently, we demonstrated highly significant antiviral activity of this HIV-1 subtype A-specific Tre in humanized mice (Hauber et al. 2013 PLOS pathogens 9:e1003587). Broad clinical application, however, requires availability of a tre-recombinase that recognizes a majority of clinical HIV-1 isolates.

Materials and methods

Here we report LTR target site identification as well as the engineering and functional analysis of a next-generation Tre-recombinase that recognizes the vast majority (e.g. >93% clade B and >80% clade A) of clinical HIV-1 isolates.

Results

It is shown that the HIV-1 LTR harbours a conserved region that may serve as a universal tre recognition site for provirus excision. In fact, targeting this site by next-generation tre-recombinase demonstrates pronounced antiviral activity in the absence of cellular toxicity.

Conclusion

The presented data suggest that next-generation Tre technology may be a valuable component of future antiretroviral therapies to reverse infection and thereby providing a cure for HIV/AIDS.

Authors’ Affiliations

(1)
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany
(2)
Department of Medical Systems Biology, University of Technology Dresden, University Hospital and Medical Faculty Carl Gustav Carus, Dresden, Germany

Copyright

© Hauber et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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