Induction of chronic human immunodeficiency virus infection is blocked in vitro by a methylphosphonate oligodeoxynucleoside targeted to a U3 enhancer element.

Abstract

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.

• Authors: J Laurence, S K Sikder, J Kulkosky, P Miller, P O Ts'o
• Journal: Journal of virology (J Virol) Vol. 65 Issue 1 Pg. 213-9 (Jan 1991) ISSN: 0022-538X [Print] United States
• PMID: 1702158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antiviral Agents
• NF-kappa B
• Oligodeoxyribonucleotides
• Oligonucleotide Probes
• dideoxyribonucleoside methylphosphonates
• RNA-Directed DNA Polymerase
• Tetradecanoylphorbol Acetate

Topics

• Antiviral Agents (pharmacology)
• Base Sequence
• Cell Line
• Cells, Cultured
• Enhancer Elements, Genetic (drug effects)
• Genes, Regulator
• Genes, Viral
• Genes, tat
• HIV Seropositivity
• HIV-1 (drug effects, genetics, physiology)
• Humans
• Molecular Sequence Data
• NF-kappa B (metabolism)
• Oligodeoxyribonucleotides (pharmacology)
• Oligonucleotide Probes
• RNA-Directed DNA Polymerase (analysis)
• Tetradecanoylphorbol Acetate
• Transcriptional Activation
• Virus Replication