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 D Rosenblatt

Research output: Contribution to journalArticle

36 Citations (Scopus)

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
Pages (from-to)928-939
Number of pages12
JournalMolecular Therapy
Volume3
Issue number6
DOIs
StatePublished - Jul 16 2001
Externally publishedYes

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HIV-1
env Genes
rev Genes
Mason-Pfizer monkey virus
HIV
Population
T-Lymphocytes
Genetic Therapy
Genes
HIV Infections
Cell Count
Macrophages

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Defective lentiviral vectors are efficiently trafficked by HIV-1 and inhibits its replication. / Klimatcheva, Ekaterina; Planelles, Vicente; Day, Shannon L.; Fulreader, Frank; Renda, Matthew J.; Rosenblatt, Joseph D.

In: Molecular Therapy, Vol. 3, No. 6, 16.07.2001, p. 928-939.

Research output: Contribution to journalArticle

Klimatcheva, Ekaterina ; Planelles, Vicente ; Day, Shannon L. ; Fulreader, Frank ; Renda, Matthew J. ; Rosenblatt, Joseph D. / Defective lentiviral vectors are efficiently trafficked by HIV-1 and inhibits its replication. In: Molecular Therapy. 2001 ; Vol. 3, No. 6. pp. 928-939.
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