Cell
Volume 63, Issue 3, 2 November 1990, Pages 601-608
Journal home page for Cell

Article
Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication

https://doi.org/10.1016/0092-8674(90)90455-NGet rights and content

Abstract

Overexpression of TAR-containing sequences (TAR decoys) was used to render cells resistant to HIV replication. A chimeric tRNAmeti-TAR transcription unit contained in a double copy murine retroviral vector was used to express high levels of HIV-1 TAR-containing transcripts in CEM SS cells. Replication of HIV-1 was inhibited over 99% in cells expressing chimeric tRNA-TAR transcripts, but an amphotropic murine retrovirus replicated normally in these cells. Expression of TAR sequences in CEM SS cells had no adverse effects on cell viability, indicating that essential cellular factors are not being sequestered in these cells. TAR decoy RNA-mediated HIV inhibition may also be effective against natural HIV isolates in spite of their hypervariable nature, as suggested by the fact that replication of SIVmac was also inhibited in cells expressing HIV-1 TAR decoys.

References (44)

  • M. Zasloff et al.

    Transcription and precursor processing of normal and mutant human tRNAmeti genes in a homologous cell-free system

    J. Biol. Chem.

    (1982)
  • S. Adeniyi-Jones et al.

    Generation of long read-through transcripts in vivo and in vitro by deletion of 3′ termination and processing sequences in the human tRNAmeti gene

    Nucl. Acids Res.

    (1984)
  • D. Armentano et al.

    Effect of internal viral sequences on the utility of retroviral vectors

    J. Virol.

    (1987)
  • D. Baltimore

    Intracellular immunization

    Nature

    (1988)
  • F. Barre-Sinoussi et al.

    Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immunodeficiency syndrome (AIDS)

    Science

    (1983)
  • J.M. Chirgwin et al.

    Isolation of biologically active ribonucleic acid from sources, enriched in ribonuclease

    Biochemistry

    (1979)
  • M. Cotten et al.

    Ribozyme mediated destruction of RNA in vivo

    EMBO J.

    (1989)
  • M.D. Daniels et al.

    Isolation of T-cell tropic HTLV-III-like retrovirus from Macaques

    Science

    (1985)
  • J. Darnell

    Macromolecules in procaryotic and eucaryotic cells

  • C. Dingwall et al.

    Human immunodeficiency virus 1 tat protein binds trans-activation-response (TAR) RNA in vitro

  • M. Emerman et al.

    The specificity of the human immunodeficiency virus type 2 transactivator is different from that of human immunodeficiency virus type 1

    EMBO J.

    (1987)
  • R. Fenrick et al.

    Functional analysis of the tat trans activator of human immunodeficiency virus type 2

    J. Virol.

    (1989)
  • Cited by (0)

    View full text