Inhibition of human immunodeficiency virus type 1 Rev-Rev-response element complex formation by complementary oligonucleotides.
Complementary 18-mer oligodeoxynucleotides (oligonucleotides) specifically inhibited the formation of human immunodeficiency virus Rev-Rev-response element (RRE) complexes. Inhibition of Rev-RRE binding required blockage of G-7819 to G-7820 in band shift assays. Structural studies revealed both local and distal effects. RRE structure was also disrupted by oligonucleotides targeted to other minor stems, by altering RNA renaturation conditions, or by reducing Rev concentrations--indicating a dynamic RRE structure and involvement of a minor RRE stem in the maturation of initial Rev-RRE complexes. Thus, complementary oligonucleotides alter RRE structure and may prove useful for the design of therapeutic anti-RRE oligonucleotides.
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Agouron Institute, La Jolla, California 92037.
D001483:Base Sequence; D004279:DNA, Viral / Q000187:drug effects / Q000378:metabolism*; D015694:Gene Products, rev / Q000187:drug effects / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009841:Oligonucleotides / Q000494:pharmacology*; D012367:RNA, Viral; D013696:Temperature; D054321:rev Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015694:Gene Products, rev; D009841:Oligonucleotides; D012367:RNA, Viral; D054321:rev Gene Products, Human Immunodeficiency Virus