Specific inhibition of human immunodeficiency virus type 1 replication by antisense oligonucleotides : an in vitro model for treatment
Identifieur interne : 004847 ( Main/Curation ); précédent : 004846; suivant : 004848Specific inhibition of human immunodeficiency virus type 1 replication by antisense oligonucleotides : an in vitro model for treatment
Auteurs : J. Lisziewicz [États-Unis] ; D. Sun [États-Unis] ; M. Klotman [États-Unis] ; S. Agrawal ; P. Zamecnik ; R. Gallo [États-Unis]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 1992.
Descripteurs français
- KwdFr :
- Cellules cultivées, Données de séquences moléculaires, Facteurs temps, Humains, Mutation, Oligonucléotides antisens (), Oligonucléotides antisens (pharmacologie), Réplication virale (), Survie cellulaire (), Séquence nucléotidique, Techniques in vitro, VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (croissance et développement), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique).
- MESH :
- croissance et développement : VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- génétique : VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- pharmacologie : Oligonucléotides antisens.
- Pascal (Inist)
- Cellules cultivées, Données de séquences moléculaires, Facteurs temps, Humains, Mutation, Oligonucléotides antisens, Réplication virale, Survie cellulaire, Séquence nucléotidique, Techniques in vitro, Virus HIV1, Antiviral, Inhibition, Infection, Modèle, Replication in vitro, Immunodéficit acquis syndrome, Spécificité, Séquence nucléotide, Chimiothérapie, Traitement, In vitro, Synthèse chimique, Mécanisme action, Lignée MOLT3, DNA antisens.
English descriptors
- KwdEn :
- AIDS, Antisense DNA, Antiviral, Base Sequence, Cell Survival (drug effects), Cells, Cultured, Chemical synthesis, Chemotherapy, HIV-1 (genetics), HIV-1 (growth & development), HIV-1 virus, Humans, In Vitro Techniques, In vitro, In vitro replication, Infection, Inhibition, Mechanism of action, Models, Molecular Sequence Data, Mutation, Nucleotide sequence, Oligonucleotides, Antisense (chemistry), Oligonucleotides, Antisense (pharmacology), Specificity, Time Factors, Treatment, Virus Replication (drug effects).
- MESH :
- chemical , chemistry : Oligonucleotides, Antisense.
- drug effects : Cell Survival, Virus Replication.
- genetics : HIV-1.
- growth & development : HIV-1.
- chemical , pharmacology : Oligonucleotides, Antisense.
- Base Sequence, Cells, Cultured, Humans, In Vitro Techniques, Molecular Sequence Data, Mutation, Time Factors.
Abstract
We have developed a culture system, simulating in vivo conditions of human immunodeficiency virus type 1 (HIV-1) injection, to evaluate the long-term efficacy of antisense oligonucleotide treatment. Five oligonucleotide phosphorothioates (28-mers), complementary to different regions of HIV-1 RNA, blocked replication of the virus in a sequence-specific manner at 1 μM concentration. Variations in antiviral activity were seen among the different oligonucleotides, invealing an effect of target selection
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Pascal:93-0236257Le document en format XML
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<term>Cells, Cultured</term>
<term>Chemical synthesis</term>
<term>Chemotherapy</term>
<term>HIV-1 (genetics)</term>
<term>HIV-1 (growth & development)</term>
<term>HIV-1 virus</term>
<term>Humans</term>
<term>In Vitro Techniques</term>
<term>In vitro</term>
<term>In vitro replication</term>
<term>Infection</term>
<term>Inhibition</term>
<term>Mechanism of action</term>
<term>Models</term>
<term>Molecular Sequence Data</term>
<term>Mutation</term>
<term>Nucleotide sequence</term>
<term>Oligonucleotides, Antisense (chemistry)</term>
<term>Oligonucleotides, Antisense (pharmacology)</term>
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<term>Virus Replication (drug effects)</term>
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<term>Mutation</term>
<term>Oligonucléotides antisens ()</term>
<term>Oligonucléotides antisens (pharmacologie)</term>
<term>Réplication virale ()</term>
<term>Survie cellulaire ()</term>
<term>Séquence nucléotidique</term>
<term>Techniques in vitro</term>
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<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Survival</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>HIV-1</term>
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<front><div type="abstract" xml:lang="en">We have developed a culture system, simulating in vivo conditions of human immunodeficiency virus type 1 (HIV-1) injection, to evaluate the long-term efficacy of antisense oligonucleotide treatment. Five oligonucleotide phosphorothioates (28-mers), complementary to different regions of HIV-1 RNA, blocked replication of the virus in a sequence-specific manner at 1 μM concentration. Variations in antiviral activity were seen among the different oligonucleotides, invealing an effect of target selection</div>
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<term>Antisense DNA</term>
<term>Antiviral</term>
<term>Chemical synthesis</term>
<term>Chemotherapy</term>
<term>HIV-1 virus</term>
<term>In vitro</term>
<term>In vitro replication</term>
<term>Infection</term>
<term>Inhibition</term>
<term>Mechanism of action</term>
<term>Models</term>
<term>Nucleotide sequence</term>
<term>Specificity</term>
<term>Treatment</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Virus HIV1</term>
<term>Antiviral</term>
<term>Inhibition</term>
<term>Infection</term>
<term>Modèle</term>
<term>Replication in vitro</term>
<term>Immunodéficit acquis syndrome</term>
<term>Spécificité</term>
<term>Séquence nucléotide</term>
<term>Chimiothérapie</term>
<term>Traitement</term>
<term>In vitro</term>
<term>Synthèse chimique</term>
<term>Mécanisme action</term>
<term>Lignée MOLT3</term>
<term>DNA antisens</term>
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<front><div type="abstract" xml:lang="en">We have developed a culture system, simulating in vivo conditions of human immunodeficiency virus type 1 (HIV-1) injection, to evaluate the long-term efficacy of antisense oligonucleotide treatment. Five oligonucleotide phosphorothioates (28-mers), complementary to different regions of HIV-1 RNA, blocked replication of the virus in a sequence-specific manner at 1 μM concentration. Variations in antiviral activity were seen among the different oligonucleotides, invealing an effect of target selection</div>
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<author><name sortKey="Lisziewicz, J" sort="Lisziewicz, J" uniqKey="Lisziewicz J" first="J" last="Lisziewicz">J. Lisziewicz</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda</wicri:cityArea>
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<author><name sortKey="Sun, D" sort="Sun, D" uniqKey="Sun D" first="D" last="Sun">D. Sun</name>
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<author><name sortKey="Klotman, M" sort="Klotman, M" uniqKey="Klotman M" first="M" last="Klotman">M. Klotman</name>
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<author><name sortKey="Zamecnik, P" sort="Zamecnik, P" uniqKey="Zamecnik P" first="P" last="Zamecnik">P. Zamecnik</name>
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<author><name sortKey="Gallo, R" sort="Gallo, R" uniqKey="Gallo R" first="R" last="Gallo">R. Gallo</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Specific inhibition of human immunodeficiency virus type 1 replication by antisense oligonucleotides: an in vitro model for treatment.</title>
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<affiliation wicri:level="2"><nlm:affiliation>Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda</wicri:cityArea>
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<author><name sortKey="Sun, D" sort="Sun, D" uniqKey="Sun D" first="D" last="Sun">D. Sun</name>
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<author><name sortKey="Klotman, M" sort="Klotman, M" uniqKey="Klotman M" first="M" last="Klotman">M. Klotman</name>
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<author><name sortKey="Agrawal, S" sort="Agrawal, S" uniqKey="Agrawal S" first="S" last="Agrawal">S. Agrawal</name>
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<author><name sortKey="Zamecnik, P" sort="Zamecnik, P" uniqKey="Zamecnik P" first="P" last="Zamecnik">P. Zamecnik</name>
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<author><name sortKey="Gallo, R" sort="Gallo, R" uniqKey="Gallo R" first="R" last="Gallo">R. Gallo</name>
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<term>Cell Survival (drug effects)</term>
<term>Cells, Cultured</term>
<term>HIV-1 (genetics)</term>
<term>HIV-1 (growth & development)</term>
<term>Humans</term>
<term>In Vitro Techniques</term>
<term>Molecular Sequence Data</term>
<term>Mutation</term>
<term>Oligonucleotides, Antisense (chemistry)</term>
<term>Oligonucleotides, Antisense (pharmacology)</term>
<term>Time Factors</term>
<term>Virus Replication (drug effects)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Cellules cultivées</term>
<term>Données de séquences moléculaires</term>
<term>Facteurs temps</term>
<term>Humains</term>
<term>Mutation</term>
<term>Oligonucléotides antisens ()</term>
<term>Oligonucléotides antisens (pharmacologie)</term>
<term>Réplication virale ()</term>
<term>Survie cellulaire ()</term>
<term>Séquence nucléotidique</term>
<term>Techniques in vitro</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (croissance et développement)</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique)</term>
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<term>Virus Replication</term>
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<term>Mutation</term>
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<term>Données de séquences moléculaires</term>
<term>Facteurs temps</term>
<term>Humains</term>
<term>Mutation</term>
<term>Oligonucléotides antisens</term>
<term>Réplication virale</term>
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<front><div type="abstract" xml:lang="en">We have developed a culture system, simulating in vivo conditions of human immunodeficiency virus type 1 (HIV-1) infection, to evaluate the long-term efficacy of antisense oligonucleotide treatment. Five oligonucleotide phosphorothioates (28-mers), complementary to different regions of HIV-1 RNA, blocked replication of the virus in a sequence-specific manner at 1 microM concentration. Variations in antiviral activity were seen among the different oligonucleotides, revealing an effect of target selection. Mismatched or random oligonucleotide phosphorothioates delayed, but did not completely inhibit, HIV-1 replication. In the case of inhibition by a splice-acceptor-site antisense oligodeoxynucleotide, a break-through phenomenon occurred after 25 days of treatment, suggesting the development of an "escape mutant." This result did not occur when the inhibitory oligodeoxynucleotides were complementary to the primary-sequence areas of the rev-responsive element and rev-1 genes. Sequential treatment of HIV-1-infected cells with a combination of different antisense oligonucleotides, each administered once, also prevented the development of escape mutants. Our results suggest that chemotherapy based on specifically targeted antisense-oligonucleotide phosphorothioates may be an effective method for reducing the viral burden in HIV-1-infected individuals at clinically achievable oligonucleotide concentrations.</div>
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