Induction of chronic human immunodeficiency virus infection is blocked in vitro by a methylphosphonate oligodeoxynucleoside targeted to a U3 enhancer element.
Oligodeoxynucleosides with internucleoside methylphosphonate linkages complementary to regions within U3 of human immunodeficiency virus type 1 were evaluated for their ability to block phorbol myristate acetate upregulation of virus in chronically infected promonocytic and T-lymphoblastoid cell lines. One such oligomer, targeted to an NF-kappa B enhancer element, inhibited phorbol myristate acetate induction of viral replication and tat-mediated trans activation of the human immunodeficiency virus long terminal repeat. The effect of this construct is contrasted with classical antisense methylphosphonate-derivatized oligomers complementary to initiation codon and splice acceptor sites of human immunodeficiency virus structural and regulatory genes. Its activity suggests a novel application of the modified oligonucleotide strategy in the blockade of viral induction from latently infected cells.
Laurence
J
J
Department of Medicine, Cornell University Medical College, New York, New York 10021.
Sikder
S K
SK
Kulkosky
J
J
Miller
P
P
Ts'o
P O
PO
D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic / Q000187:drug effects*; D005809:Genes, Regulator; D005814:Genes, Viral; D015756:Genes, tat; D006679:HIV Seropositivity; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D015345:Oligonucleotide Probes; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate; D015533:Transcriptional Activation; D014779:Virus Replication
D000998:Antiviral Agents; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; C021992:dideoxyribonucleoside methylphosphonates; D012194:RNA-Directed DNA Polymerase; D013755:Tetradecanoylphorbol Acetate