Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication.
Overexpression of TAR-containing sequences (TAR decoys) was used to render cells resistant to HIV replication. A chimeric tRNA(meti)-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.
Sullenger
B A
BA
Program of Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Gallardo
H F
HF
Ungers
G E
GE
Gilboa
E
E
D001483:Base Sequence; D002460:Cell Line; D005822:Genetic Vectors; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012358:RNA, Transfer, Met / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D014158:Transcription, Genetic; D014779:Virus Replication
D015345:Oligonucleotide Probes; D012358:RNA, Transfer, Met; D012367:RNA, Viral