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PMID: 1702158 Published · ppublish English 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.

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

Journal of virology ·Vol. 65 ·No. 1 ·1991-01-00 ·Pages 213-9

Laurence J, Sikder SK, Kulkosky J, Miller P, Ts'o PO

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.

MeSH Terms
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
Chemicals
Antiviral Agents NF-kappa B Oligodeoxyribonucleotides Oligonucleotide Probes dideoxyribonucleoside methylphosphonates RNA-Directed DNA Polymerase Tetradecanoylphorbol Acetate
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Laurence J
Department of Medicine, Cornell University Medical College, New York, New York 10021.
Sikder S K
Kulkosky J
Miller P
Ts'o P O
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.65.1.213-219.1991
Published
1991-01-00
Pages
213-9
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC240507
Subset
IM
Grants
NIAID NIH HHS · AI29119 · United States
NCI NIH HHS · CA42762 · United States
NIGMS NIH HHS · GM31927 · United States
External Links
PubMed source DOI: 10.1128/JVI.65.1.213-219.1991 PMC Full Text View journal details
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