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  • Title: Inhibition of HIV-1 replication in primary human T cells transduced with an intracellular anti-HIV-1 p17 antibody gene.
    Author: Tewari D, Notkins AL, Zhou P.
    Journal: J Gene Med; 2003 Mar; 5(3):182-9. PubMed ID: 12666184.
    Abstract:
    BACKGROUND: Previously we reported that human CD4(+) T cell lines stably expressing anti-HIV-1 gag p17 scFv/Ckappa in the cytosol or nucleus were resistant to HIV-1 challenge. Inhibition of HIV-1 by anti-HIV-1 gag p17 scFv/Ckappa occurred at both the pre- and post-integration steps of the viral cycle. To simulate more closely the in vivo infection process, in this study we tested anti-HIV-1 activity of anti-HIV-1 gag p17 scFv/Ckappa in primary human T cells. METHODS: Anti-HIV-1 gag p17 scFv/Ckappa gene that is targeted into cytoplasm was inserted into a MMLV vector and transfected into packaging cell line PT67. The recombinant virus was used to transduce primary human T cells and human CD4(+) T cell line Jurkat. Following transduction, transduction efficiency, transgene expression, and cell phenotypes were studied. Transduced cells were then challenged with 100 TCID(50) of HIV-1 IIIB and primary isolate 5AO12. Following challenge, HIV-1 replication was monitored by p24 production. RESULTS: Both transduced Jurkat and primary human T cells expressed the transgene. The expression of the transgene did not alter cell growth and CD4 or CD8 expression. However, HIV-1 replication in scFv/Ckappa-transduced Jurkat cells was inhibited by nearly 90% as compared with vector controls. More importantly, HIV-1 replication in primary human T cells from multiple donors transduced with the anti-HIV-1 gag p17 scFv/Ckappa gene was inhibited by as much as 99% as compared with primary T cells transduced with the vector control. The inhibition of replication was not due to interference in viral entry or reverse transcription. The less that HIV-1 replicated in different donor cells, the higher the degree of protection. CONCLUSIONS: The expression of the anti-HIV-1 gag p17 scFv/Ckappa gene construct in primary human T cells renders these cells resistant to HIV-1 and points to the potential clinical usefulness of this gene construct for anti-HIV-1 gene therapy.
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