Foamy virus vectors expressing anti-HIV transgenes efficiently block HIV-1 replication

Jason A. Taylor, Lucia Vojtech, Ingrid Bahner, Donald B. Kohn, Dorothee Von Laer, David W. Russell, Robert E. Richard

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Gene therapy has the potential to control human immunodeficiency virus (HIV) in patients who do not respond to traditional antiviral therapy. In this study, we tested foamy virus (FV) vectors expressing three anti-HIV transgenes, both individually and in a combination vector. The transgenes tested in this study are RevM10, a dominant negative version of the viral rev protein, Sh1, a short hairpin RNA directed against a conserved overlapping sequence of tat and rev, and membrane-associated C46 (maC46), a membrane-attached peptide that blocks HIV cell entry. FV vectors efficiently transduce hematopoietic stem cells and, unlike lentivirus (LV) vectors, do not share viral proteins with HIV. The titers of the FV vectors described in this study were not affected by anti-HIV transgenes. On a direct comparison of FV vectors expressing the individual transgenes, entry inhibition using the maC46 transgene was found to be the most effective at blocking HIV replication. A clinically relevant FV vector expressing three anti-HIV transgenes effectively blocked HIV infection in primary macrophages derived from transduced, peripheral blood CD34-selected cells and in a cell line used for propagating HIV, CEM×174. These results suggest that there are potential benefits of using FV vectors in HIV gene therapy.

Original languageEnglish (US)
Pages (from-to)46-51
Number of pages6
JournalMolecular Therapy
Volume16
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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