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Lentiviral transduction of human T-lymphocytes with a RANTES intrakine inhibits human immunodeficiency virus type 1 infection

Gene Therapy volume 9, pages 889–897 (2002)Cite this article

Abstract

Intrakines, modified intracellular chemokines, offer a novel strategy to prevent cellular entry of HIV-1 by blocking the surface expression of HIV-1 co-receptors. To investigate potential clinical applications of the RANTES-intrakine, we explored the use of HIV-1-based lentiviral vectors for therapeutic gene transfer into T-lymphocytes. RANTES-intrakine genes can be efficiently transduced into primary human T-lymphocytes by lentiviral vectors, especially when human T-lymphocytes were stimulated with CD3 and CD28 antibodies. The transduced T cells showed decreased surface expression of the chemokine receptor CCR-5, as well as CCR-1 and CCR-3. This lentivirus-mediated approach to intrakine gene transfer protected human T-lymphocytes from infection by a variety of R5-tropic HIV-1 strains. A quantitative real-time PCR assay, developed to monitor cells for HIV entry and persistence, revealed persistent low copy numbers of proviral HIV DNA in RANTES intrakine-transduced T-lymphocytes during 3-week culture, suggesting that viruses produced from infected untransduced cell populations were unable to infect the surrounding transduced T-lymphocytes. We conclude that targeting HIV-1 co-receptors to block virus entry with lentiviral vectors is an attractive approach to the control of HIV-1 infection.

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Acknowledgements

We thank Mike Cubbage for technical assistance with the MoFlo cell sorting. Also we wish to thank D Trono (University of Geneva) and P Charneaux (Institut Pasteur, Paris) for providing plasmid vectors. We would like to thank Malcolm K Brenner for critical review of the manuscript. This work was supported by a NIH grant R01-AI48480 (S-Y Chen). R Schroers and H-J Wagner were in part supported by the Deutsche Forschungsgemeinschaft (DFG, Schr 629/1-1, Wa 1149/2-1). CM Davis was in part supported by a NIH fellowship.

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Authors and Affiliations

  1. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA

    R Schroers, CM Davis, H-J Wagner & S-Y Chen

  2. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    R Schroers, CM Davis & H-J Wagner

  3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    S-Y Chen

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  1. R Schroers
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Schroers, R., Davis, C., Wagner, HJ. et al. Lentiviral transduction of human T-lymphocytes with a RANTES intrakine inhibits human immunodeficiency virus type 1 infection. Gene Ther 9, 889–897 (2002). https://doi.org/10.1038/sj.gt.3301711

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