Poly(L-lysine)-conjugated oligonucleotides promote sequence-specific inhibition of acute HIV-1 infection
Previously, we have reported that conjugation of antisense oligonucleotides to poly(L-lysine) (PLL) lowers their inhibitory concentration in several biological models. We have now tested these conjugates for inhibition of human immunodeficiency virus type 1 (HIV-1) replication. PLL-conjugated oligonucleotides complementary to the translation initiation site of Tat protein protect cells from the cytopathic effect of HIV-1 in acute infection assays. The EC50 of conjugates is approximately 0.15 microM, which represents a strong reduction in concentration as compared to nonconjugated oligonucleotides (EC50 = 20 microM). In contrast with most reports in the literature, we have observed sequence specific antiviral effects with PLL conjugates. This was particularly noteworthy in antiviral experiments performed with HIV-1 isolates presenting heterogeneity in the 5' end of the tat mRNA sequence. Two mismatches at the target site were sufficient to reduce very significantly the antiviral activity of the conjugates but did not modify the effect of nonconjugated oligonucleotides. Unlike free oligonucleotides, PLL-conjugated ones do not interfere with virus penetration and/or reverse transcription as demonstrated by polymerase chain reaction (PCR) analysis of viral DNA.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1992 |
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| Erschienen: |
1992 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:2 |
|---|---|
| Enthalten in: |
Antisense research and development - 2(1992), 4 vom: 25., Seite 293-301 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Degols, G [VerfasserIn] |
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| Anmerkungen: |
Date Completed 02.04.1993 Date Revised 28.10.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM012645672 |
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| 041 | |a eng | ||
| 100 | 1 | |a Degols, G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Poly(L-lysine)-conjugated oligonucleotides promote sequence-specific inhibition of acute HIV-1 infection |
| 264 | 1 | |c 1992 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 02.04.1993 | ||
| 500 | |a Date Revised 28.10.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Previously, we have reported that conjugation of antisense oligonucleotides to poly(L-lysine) (PLL) lowers their inhibitory concentration in several biological models. We have now tested these conjugates for inhibition of human immunodeficiency virus type 1 (HIV-1) replication. PLL-conjugated oligonucleotides complementary to the translation initiation site of Tat protein protect cells from the cytopathic effect of HIV-1 in acute infection assays. The EC50 of conjugates is approximately 0.15 microM, which represents a strong reduction in concentration as compared to nonconjugated oligonucleotides (EC50 = 20 microM). In contrast with most reports in the literature, we have observed sequence specific antiviral effects with PLL conjugates. This was particularly noteworthy in antiviral experiments performed with HIV-1 isolates presenting heterogeneity in the 5' end of the tat mRNA sequence. Two mismatches at the target site were sufficient to reduce very significantly the antiviral activity of the conjugates but did not modify the effect of nonconjugated oligonucleotides. Unlike free oligonucleotides, PLL-conjugated ones do not interfere with virus penetration and/or reverse transcription as demonstrated by polymerase chain reaction (PCR) analysis of viral DNA | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a DNA, Viral |2 NLM | |
| 650 | 7 | |a Gene Products, tat |2 NLM | |
| 650 | 7 | |a Oligonucleotides, Antisense |2 NLM | |
| 650 | 7 | |a tat Gene Products, Human Immunodeficiency Virus |2 NLM | |
| 650 | 7 | |a Polylysine |2 NLM | |
| 650 | 7 | |a 25104-18-1 |2 NLM | |
| 650 | 7 | |a HIV Reverse Transcriptase |2 NLM | |
| 650 | 7 | |a EC 2.7.7.49 |2 NLM | |
| 650 | 7 | |a RNA-Directed DNA Polymerase |2 NLM | |
| 650 | 7 | |a EC 2.7.7.49 |2 NLM | |
| 700 | 1 | |a Leonetti, J P |e verfasserin |4 aut | |
| 700 | 1 | |a Benkirane, M |e verfasserin |4 aut | |
| 700 | 1 | |a Devaux, C |e verfasserin |4 aut | |
| 700 | 1 | |a Lebleu, B |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Antisense research and development |d 1993 |g 2(1992), 4 vom: 25., Seite 293-301 |w (DE-627)NLM012638110 |x 1050-5261 |7 nnns |
| 773 | 1 | 8 | |g volume:2 |g year:1992 |g number:4 |g day:25 |g pages:293-301 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 2 |j 1992 |e 4 |b 25 |h 293-301 | ||