Expression of the human immunodeficiency virus type 1 primer binding sequence inhibits HIV-1 replication

Amer M. Kechli, Pamela J. Freiden, John J. Rossi, Malcolm K. Brenner, Mona A. Choueiry, J. Victor Garcia, Karen S. Slobod

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Optimal targets for anti-human immunodeficiency virus (HIV) moieties are those regions of the viral genome that are greatly conserved. The primer binding site (PBS) of HIV is an 18-nucleotide sequence complementary to the 3' end of tRNA(Lys3) that serves as the primer for HIV-1 reverse transcription, All HIV-1 isolates analyzed to date contain a PBS complementary to tRNA(Lys3) illustrating the conservation of this sequence, We investigated the activity of a hammerhead ribozyme targeting the PBS of HIV-1, CEMss cells transduced with retroviral vectors containing either the PBS hammerhead ribozyme or its complementary sequence (as a control) in the R region of the vector long terminal repeat (LTR) were challenged with HIV-1(NL4-3). Surprisingly > 80% inhibition of HIV-1 production was observed with the vector containing the (control) sequence complementary to the PBS ribozyme. We propose that the LTR-driven vector transcript containing 18 nucleotides identical to the HIV-1 PBS may act like an RNA decoy to titrate viral proteins such as reverse transcriptase and nucleocapsid away from genuine viral transcripts, thus compromising virus replication.

Original languageEnglish (US)
Pages (from-to)587-590
Number of pages4
JournalHuman Gene Therapy
Volume9
Issue number4
DOIs
StatePublished - Mar 1 1998

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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