Suppression of HIV-1 infection in primary CD4 T cells transduced with a self-inactivating lentiviral vector encoding a membrane expressed gp41-derived fusion inhibitor

E. E. Perez, J. L. Riley, R. G. Carroll, D. Von Laer, C. H. June

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Peptidomimetics of HIV-1 gp41 sequences required for membrane fusion are potent inhibitors of HIV-1 entry. We hypothesize that expression of a membrane-bound gp41-derived fusion inhibitor will confer HIV-1 resistance to primary CD4 T cells. Efficient gene delivery and stable expression of a membrane-bound gp41-derived fusion inhibitor to primary CD4 T cells was accomplished using a self-inactivating lentiviral vector. A potent antiviral effect was observed when transduced CD4 T cells were challenged with a highly virulent CXCR4-tropic strain of HIV-1. Production of soluble p24 in the supernatant was inhibited 100-fold, and cytopathic effects were evident early in non-transduced cells and absent in transduced cells. Expression of the gp41 sequences was not detrimental to CD4 cells as transduced CD4 T cells exhibited a population doubling time that was equivalent to T cells transduced with a control vector. Results from this study support the rationale to use this lentiviral vector targeted at HIV entry as a potential gene therapy for HIV infection.

Original languageEnglish
Pages (from-to)26-32
Number of pages7
JournalClinical Immunology
Volume115
Issue number1 SPEC. ISS.
DOIs
StatePublished - Apr 1 2005

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Keywords

  • Adoptive therapy
  • Gene therapy
  • gp41
  • HIV-1 infection

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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