Defective lentiviral vectors are efficiently trafficked by HIV-1 and inhibits its replication

Ekaterina Klimatcheva, Vicente Planelles, Shannon L. Day, Frank Fulreader, Matthew J. Renda, Joseph Rosenblatt

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Gene therapy against HIV infection should involve vector-mediated delivery of anti-HIV therapeutic genes into T-lymphocytes and macrophages or, alternatively, hematopoietic progenitors. Transduction of mature cells with defective vectors would have limited success because the vector would disappear with cell turnover. However, if a vector could be trafficked by wild-type HIV, initial transduction of a majority of the population would not be required, as the vector would be able to spread. We describe HIV-1-based lentiviral vectors that are efficiently packaged and trafficked by HIV-1, allowing a small number of cells initially transduced to spread the vector within a nontransduced cell population. We examined whether the presence or absence of the rev gene and the Rev-responsive element (RRE) would have a noticeable effect on the ability of lentiviral vectors to be trafficked and to inhibit HIV-1 replication. We found that replacement of rev/RRE with a constitutive transport element from Mason-Pfizer monkey virus had no apparent effect on trafficking and did not change the intrinsic inhibitory abilities of the vectors. We also constructed a rev/RRE-independent HIV-1-derived vector carrying a trans-dominant negative mutant of HIV-1 Rev, RevM10. This vector was less efficiently trafficked by HIV-1 and, despite the presence of an anti-HIV-1 gene, RevM10, was less efficient at inhibiting HIV-1 replication when introduced into a target T-cell population.

Original languageEnglish (US)
Pages (from-to)928-939
Number of pages12
JournalMolecular Therapy
Volume3
Issue number6
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

ASJC Scopus subject areas

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

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