Overexpression of RRE-derived sequences inhibits HIV-1 replication in CEM cells.
Overexpression of sequences corresponding to the major Rev-binding site in the Rev response element of human immunodeficiency virus type 1 (HIV-1) (RRE decoys) was used to render cells resistant to HIV-1 replication. This was accomplished by the use of a chimeric tRNA-RRE transcription unit in a double-copy murine retroviral vector to express high levels of HIV-1 RRE-containing transcripts in CEM SS cells. Replication of HIV-1 was inhibited more than 90% in cells expressing chimeric tRNA-RRE transcripts, as determined by in situ immunofluorescence analysis and a p24 antigen ELISA test. Analysis of RNA from HIV-1-infected cells suggests that expression of RRE-containing sequences in CEM SS cells inhibits HIV-1 replication by interfering with Rev function, presumably by competing for Rev binding to its physiological target. The use of a subfragment of RRE as decoy RNA reduces the likelihood that essential cellular factors will be sequestered in cells expressing the decoy RNA. Thus, use of RRE-based decoy RNA to inhibit HIV-1 replication may represent a safer alternative to the use of TAR decoy RNA.
Lee
T C
TC
Sloan-Kettering Institute, New York, NY 10021.
Sullenger
B A
BA
Gallardo
H F
HF
Ungers
G E
GE
Gilboa
E
E
D001483:Base Sequence; D002460:Cell Line; D015757:Genes, rev / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D012343:RNA, Transfer / Q000502:physiology; D012367:RNA, Viral / Q000502:physiology; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics*
D012367:RNA, Viral; D012343:RNA, Transfer