Conditional expression of α1-antitrypsin delivered by recombinant sv40 vectors protects lymphocytes against hiv

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. Access through your institution Buy or subscribe This is a preview of subscription content,

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Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pathology, Jefferson Medical College, Philadelphia, PA, USA P Cordelier & D S Strayer Authors * P

Cordelier View author publications You can also search for this author inPubMed Google Scholar * D S Strayer View author publications You can also search for this author inPubMed Google

Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 08 January 2003 * Accepted: 09 May 2003 *

Published: 17 November 2003 * Issue Date: 01 December 2003 * DOI: https://doi.org/10.1038/sj.gt.3302113 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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KEYWORDS * α1-antitrypsin * SV40 * conditional promoter