Phosphorothioate oligonucleotides inhibit the replication of lentiviruses and type D retroviruses, but not that of type C retroviruses
Identifieur interne : 001A49 ( Istex/Checkpoint ); précédent : 001A48; suivant : 001A50Phosphorothioate oligonucleotides inhibit the replication of lentiviruses and type D retroviruses, but not that of type C retroviruses
Auteurs : D. Archambault [Canada] ; C. A. Stein [États-Unis] ; J. S. Cohen [États-Unis]Source :
- Archives of Virology [ 0304-8608 ] ; 1994-03-01.
English descriptors
- Teeft :
- Acad, Amphotropic strain, Analog, Anemia virus, Antiviral, Antiviral activity, Antiviral effect ofphosphorothioate oligonucleotides, Archambault, Assay, Base composition, Caev, Caev probe, Caprine arthritis encephalitis virus, Cell culture, Cell culture supernatants, Cell cultures, Culture supernatants, Dextran sulfate, Different retroviruses, Eiav, Equine dermis cells, Full length, Gene expression, Herpes simplex, Himalayan, Himalayan tahr cells, Himalayan tahr ovary cells, Human immunodeficiency virus, Human immunodeficiencyvirus type, Inhibition, Inhibitor, Inhibitory effect, Lentivirus replication, Lentiviruses, Mitogenic, Mitogenic assay, Mitogenic indices, Mulv, Natl, Normal oligonucleotides, Nuclease digestion, Oligodeoxynucleotides, Oligonucleotide, Oligonucleotide analogs, Oligonucleotides, Oligos, Other cell types, Ovary, Phosphorothioate, Phosphorothioate analogs, Phosphorothioate oligodeoxynucleotides, Phosphorothioate oligonucleotides, Present data, Proc, Proc natl acad, Protease inhibitors, Replication, Retrovirus, Same cell line, Serial dilutions, Simian type, Simplex type, Smrv, Southern blot analysis, Tahr, Tahr cells, Tahr ovary cells, Test compounds, Thymus cells, Transcriptase, Viral, Viral expression, Viral genome, Virus, Virus absorption, Virus absorption period, Virus attachment, Virus inoculum, Virus replication, Virus titer, Weeks post infection.
Abstract
Summary: Phosphorothioate analogs of oligodeoxynucleotides at a concentration of 2µM protected Himalayan tahr cells from infection by caprine arthritis encephalitis virus (CAEV) and equine dermis cells from infection by equine infectious anemia virus (EIAV). The characteristics of this inhibition against these lentiviruses are similar to those previously described for the inhibition of HIV-1 in ATH8 cells [17]. Thus, the 28-mer homo-oligomer of cytidine [S-(dC)28] was at least as effective as three anti-sense sequences targeted to the LTR,gag, andenv regions of CAEV. The effectiveness of homo-oligomers of equal length was in the order C>>A>T, and a random 28-copolymer with a composition of 2C:1G was as effective as S-(dC)28. Shorter oligonucleotides were less effective (28>14>5 mers) for all base compositions tested. While replication of a simian type D retrovirus was inhibited by S-(dC)28, this compound did not inhibit the cytopathogenicity of two type C retroviruses, amphotropic murine leukemia virus (MuLV), and baboon endogenous virus, when they were tested in the same cell lines used to support the replication of lentiviruses. Southern blot analysis of the high molecular weight DNA of drug-treated CAEV-infected cells showed that S-(dC)28 was acting at or before the reverse transcription step. Our present data and the earlier finding that S-(dC)28 is a potent in vitro inhibitor of the MuLV reverse transcriptase [15] suggest that S-(dC)28 is acting very early in the replication cycle of these lentiviruses. Since MuLV reverse transcriptase is inhibited in vitro, but its replication is not blocked in permissive cells, our data suggest that the phosphorothioate oligonucleotides are preventing virus attachment.
Url:
DOI: 10.1007/BF01309457
Affiliations:
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Archambault</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>Departement des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec</wicri:regionArea><orgName type="university">Université du Québec à Montréal</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Stein, C A" sort="Stein, C A" uniqKey="Stein C" first="C. A." last="Stein">C. A. Stein</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>College of Physicians and Surgeons, Columbia University, New York</wicri:cityArea></affiliation></author><author><name sortKey="Cohen, J S" sort="Cohen, J S" uniqKey="Cohen J" first="J. S." last="Cohen">J. S. Cohen</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology, Georgetown University Medical School, Rockville, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Archives of Virology</title><title level="j" type="abbrev">Archives of Virology</title><idno type="ISSN">0304-8608</idno><idno type="eISSN">1432-8798</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Vienna</pubPlace><date type="published" when="1994-03-01">1994-03-01</date><biblScope unit="volume">139</biblScope><biblScope unit="issue">1-2</biblScope><biblScope unit="page" from="97">97</biblScope><biblScope unit="page" to="109">109</biblScope></imprint><idno type="ISSN">0304-8608</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0304-8608</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Acad</term><term>Amphotropic strain</term><term>Analog</term><term>Anemia virus</term><term>Antiviral</term><term>Antiviral activity</term><term>Antiviral effect ofphosphorothioate oligonucleotides</term><term>Archambault</term><term>Assay</term><term>Base composition</term><term>Caev</term><term>Caev probe</term><term>Caprine arthritis encephalitis virus</term><term>Cell culture</term><term>Cell culture supernatants</term><term>Cell cultures</term><term>Culture supernatants</term><term>Dextran sulfate</term><term>Different retroviruses</term><term>Eiav</term><term>Equine dermis cells</term><term>Full length</term><term>Gene expression</term><term>Herpes simplex</term><term>Himalayan</term><term>Himalayan tahr cells</term><term>Himalayan tahr ovary cells</term><term>Human immunodeficiency virus</term><term>Human immunodeficiencyvirus type</term><term>Inhibition</term><term>Inhibitor</term><term>Inhibitory effect</term><term>Lentivirus replication</term><term>Lentiviruses</term><term>Mitogenic</term><term>Mitogenic assay</term><term>Mitogenic indices</term><term>Mulv</term><term>Natl</term><term>Normal oligonucleotides</term><term>Nuclease digestion</term><term>Oligodeoxynucleotides</term><term>Oligonucleotide</term><term>Oligonucleotide analogs</term><term>Oligonucleotides</term><term>Oligos</term><term>Other cell types</term><term>Ovary</term><term>Phosphorothioate</term><term>Phosphorothioate analogs</term><term>Phosphorothioate oligodeoxynucleotides</term><term>Phosphorothioate oligonucleotides</term><term>Present data</term><term>Proc</term><term>Proc natl acad</term><term>Protease inhibitors</term><term>Replication</term><term>Retrovirus</term><term>Same cell line</term><term>Serial dilutions</term><term>Simian type</term><term>Simplex type</term><term>Smrv</term><term>Southern blot analysis</term><term>Tahr</term><term>Tahr cells</term><term>Tahr ovary cells</term><term>Test compounds</term><term>Thymus cells</term><term>Transcriptase</term><term>Viral</term><term>Viral expression</term><term>Viral genome</term><term>Virus</term><term>Virus absorption</term><term>Virus absorption period</term><term>Virus attachment</term><term>Virus inoculum</term><term>Virus replication</term><term>Virus titer</term><term>Weeks post infection</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Summary: Phosphorothioate analogs of oligodeoxynucleotides at a concentration of 2µM protected Himalayan tahr cells from infection by caprine arthritis encephalitis virus (CAEV) and equine dermis cells from infection by equine infectious anemia virus (EIAV). The characteristics of this inhibition against these lentiviruses are similar to those previously described for the inhibition of HIV-1 in ATH8 cells [17]. Thus, the 28-mer homo-oligomer of cytidine [S-(dC)28] was at least as effective as three anti-sense sequences targeted to the LTR,gag, andenv regions of CAEV. The effectiveness of homo-oligomers of equal length was in the order C>>A>T, and a random 28-copolymer with a composition of 2C:1G was as effective as S-(dC)28. Shorter oligonucleotides were less effective (28>14>5 mers) for all base compositions tested. While replication of a simian type D retrovirus was inhibited by S-(dC)28, this compound did not inhibit the cytopathogenicity of two type C retroviruses, amphotropic murine leukemia virus (MuLV), and baboon endogenous virus, when they were tested in the same cell lines used to support the replication of lentiviruses. Southern blot analysis of the high molecular weight DNA of drug-treated CAEV-infected cells showed that S-(dC)28 was acting at or before the reverse transcription step. Our present data and the earlier finding that S-(dC)28 is a potent in vitro inhibitor of the MuLV reverse transcriptase [15] suggest that S-(dC)28 is acting very early in the replication cycle of these lentiviruses. Since MuLV reverse transcriptase is inhibited in vitro, but its replication is not blocked in permissive cells, our data suggest that the phosphorothioate oligonucleotides are preventing virus attachment.</div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Maryland</li><li>Québec</li><li>État de New York</li></region><settlement><li>Montréal</li></settlement><orgName><li>Université du Québec à Montréal</li></orgName></list><tree><country name="Canada"><region name="Québec"><name sortKey="Archambault, D" sort="Archambault, D" uniqKey="Archambault D" first="D." last="Archambault">D. Archambault</name></region></country><country name="États-Unis"><region name="État de New York"><name sortKey="Stein, C A" sort="Stein, C A" uniqKey="Stein C" first="C. A." last="Stein">C. A. Stein</name></region><name sortKey="Cohen, J S" sort="Cohen, J S" uniqKey="Cohen J" first="J. S." last="Cohen">J. S. 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