Abstract:
:We investigated a strategy for gene therapy, intracellular expression of anti-HIV-1 Rev single-chain variable fragments (SFvs), in promonocytic (U1) and T (ACH-2) cell lines latently infected with HIV-1. The cellular and molecular mechanisms leading to activation of latent integrated HIV-1 provirus in U1 and ACH-2 cells have been well delineated. These cells produce HIV-1 in response to stimulation with certain cytokines. U1 and ACH-2 cells were transduced with a murine retroviral shuttle vector that expresses anti-Rev SFv (pLXSN-D8SFv-Rev) or with a control murine leukemia virus (MLV) vector (pLXSN). Tumor necrosis factor alpha (TFNalpha)-, interleukin 6 (IL-6)-, and phorbol myristate acid (PMA)-induced HIV-1 expression, as determined by reverse transcriptase (RT) assay, was significantly inhibited in cells transduced with pLXSN-D8SFv-Rev, compared with cells transduced with pLXSN. In addition, pLXSN-D8SFv-Rev-transduced cells, when incubated with monokine-enriched supernatants of human peripheral blood monocyte cultures, produced significantly less HIV-1 than did cells transduced with pLXSN. This resistance to cytokine-induced HIV-1 expression was demonstrated in SFv-transduced U1 and ACH-2 cells maintained in G418-free medium for 2 months. These data suggest that feasibility of utilizing various anti-HIV-1 SFvs to block activation of HIV-1 infection in vivo.
journal_name
AIDS Res Hum Retrovirusesjournal_title
AIDS research and human retrovirusesauthors
Ho WZ,Lai JP,Bouhamdan M,Duan L,Pomerantz RJ,Starr SEdoi
10.1089/aid.1998.14.1573subject
Has Abstractpub_date
1998-11-20 00:00:00pages
1573-80issue
17eissn
0889-2229issn
1931-8405journal_volume
14pub_type
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journal_title:AIDS research and human retroviruses
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journal_title:AIDS research and human retroviruses
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journal_title:AIDS research and human retroviruses
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journal_title:AIDS research and human retroviruses
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journal_title:AIDS research and human retroviruses
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journal_title:AIDS research and human retroviruses
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journal_title:AIDS research and human retroviruses
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journal_title:AIDS research and human retroviruses
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journal_title:AIDS research and human retroviruses
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journal_title:AIDS research and human retroviruses
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