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