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- W2084401260 abstract "Several lines of evidence suggest a potential major role for interferon (IFN) in controlling HIV-1 replication. However, this inhibition is moderate and is reversible upon IFN removal. To achieve prolonged high concentrations of IFN at the site of infection, we devised an SV40-based vector, SV[HIVLTR]IFN, to direct the synthesis of human IFN-alpha2, by employing a virus-trans-activated human IFN-alpha2 gene to be transcribed in response to HIV-1 infection. Expression of IFN-alpha2 was confirmed by Northern and Western blotting, in SV[HIVLTR]IFN-transduced, HIV-1-challenged human lymphocyte lines and primary human lymphocytes. SV[HIVLTR]IFN-transduced cells showed no evidence of HIV-1-related cytophatic effects when challenged with high doses of HIV-1(NL4-3). As measured by supernatant HIV-1 p24 antigen concentration, IFN-alpha2-expressing cell lines and peripheral blood lymphocytes (PBL) were protected from high-dose challenges of HIV-1. rSV40-delivered IFN-alpha2 inhibited gp120 protein synthesis and expression of HIV-1 mRNAs. Finally, Southern analysis revealed that levels of proviral DNA were markedly reduced in SV[HIVLTR]IFN-transduced cells compared to control cultures. IFN-alpha2 expression driven by HIVLTR delivered by an rSV40 vector thus strongly inhibits HIV-1 replication, probably by blocking a preintegration step in HIV-1 infection. Targeted expression of IFN-alpha2 delivered by SV40 can thus repress HIV-1 replication, and may be a useful approach to HIV-1 treatment." @default.
- W2084401260 created "2016-06-24" @default.
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- W2084401260 date "2002-10-01" @default.
- W2084401260 modified "2023-09-27" @default.
- W2084401260 title "Trans-Activated Interferon-α2 Delivered to T Cells by SV40 Inhibits Early Stages in the HIV-1 Replicative Cycle" @default.
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- W2084401260 doi "https://doi.org/10.1089/152581602760404621" @default.
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