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Conditional expression of α1-antitrypsin delivered by recombinant SV40 vectors protects lymphocytes against HIV

Gene Therapy volume 10, pages 2153–2156 (2003)Cite this article

Abstract

Constitutive expression of α1-antitrypsin (α1AT), a serine protease inhibitor, by a recombinant simian virus-40-based vector blocks both HIV gp160 and p55 processing, and so is a powerful inhibitor of HIV replication. To apply these findings more effectively in devising HIV therapies, we tested HIV LTR conditional promoter, to drive the expression of α1AT. SV[LTR](AT) was designed so that synthesis of human α1AT would be trans-activated by HIV infection. Cell lines and primary human lymphocytes were transduced with SV[LTR](AT) without selection and detectable toxicity. Responsiveness of α1AT expression to HIV Tat or HIV challenge was confirmed by Northern blotting, RT-PCR, cytofluorimetry and immunostaining. SV[LTR](AT)-transduced cells were protected from HIV-1NL4-3 at a challenge dose of 0.04 MOI (T-cell lines) or 0.2 MOI (peripheral blood lymphocytes). Conditional expression of α1AT consistently protected T cells from HIV challenge as effectively as did constitutive expression. Combining the efficiency of rSV40 vectors with HIV-responsive expression of a highly effective anti-HIV therapeutic may be an effective approach to gene therapy of HIV replication.

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  1. Department of Pathology, Jefferson Medical College, Philadelphia, PA, USA

    P Cordelier & D S Strayer

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  1. P Cordelier
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  2. D S Strayer
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Cordelier, P., Strayer, D. Conditional expression of α1-antitrypsin delivered by recombinant SV40 vectors protects lymphocytes against HIV. Gene Ther 10, 2153–2156 (2003). https://doi.org/10.1038/sj.gt.3302113

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  • DOI: https://doi.org/10.1038/sj.gt.3302113

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