Trans-activated interferon-α2 delivered to T cells by SV40 inhibits early stages in the HIV-1 replicative cycle

Pierre Cordelier, Sandra A. Calarota, David S. Strayer

Research output: Contribution to journalArticlepeer-review

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-α2, by employing a virus-trans-activated human IFN-α2 gene to be transcribed in response to HIV-1 infection. Expression of IFN-α2 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-α2-expressing cell lines and peripheral blood lymphocytes (PBL) were protected from high-dose challenges of HIV-1. rSV40-delivered IFN-α2 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-α2 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-α2 delivered by SV40 can thus repress HIV-1 replication, and may be a useful approach to HIV-1 treatment.

Original languageEnglish
Pages (from-to)817-828
Number of pages12
JournalJournal of Hematotherapy and Stem Cell Research
Volume11
Issue number5
DOIs
Publication statusPublished - Oct 2002

ASJC Scopus subject areas

  • Hematology
  • Immunology

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