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Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Penetration into Target Cells by Synthetic Peptides Mimicking the N-Terminus of the HIV-1 Transmembrane Glycoprotein

Identifieur interne : 004650 ( Main/Exploration ); précédent : 004649; suivant : 004651

Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Penetration into Target Cells by Synthetic Peptides Mimicking the N-Terminus of the HIV-1 Transmembrane Glycoprotein

Auteurs : Vladimir A. Slepushkin [Russie] ; Galina V. Kornilaeva [Russie] ; Sergei M. Andreev [Russie] ; Maria V. Sidorova [Russie] ; Anna O. Petrukhina [Russie] ; Gennady R. Matsevich [Russie] ; Svetlana V. Raduk [Russie] ; Vladimir B. Grigoriev [Russie] ; Tatiana V. Makarova [Russie] ; Vladimir V. Lukashov [Russie] ; Edvard V. Karamov [Russie]

Source :

RBID : ISTEX:3EE0927BA7F0F6F5A5B879E6A2415EE329175B71

Abstract

Abstract: To investigate the mechanism of action of the 22-amino-acid HIV fusion peptide on HIV infection, we studied its influence on virus adsorption and HIV-induced syncytium formation. The effect of the peptide preparations on the synthesis of viral antigens in HIV-infected cell cultures was determined by antigen capture assay, and the inhibition of proviral DNA synthesis was detected by hybridization with a HIV-specific oligonucleotide probe after PCR amplification. Fusion peptides inhibited HIV-induced syncytium formation and antigen production in lyric infected cells, and this effect was increased in conjugation with bovine serum albumin or with synthetic net-charged polymer by its C-terminus. The association of peptide with carrier by N-terminus, or with positive-charged polymer or gelatin completely abolished its effect on HIV infection. No peptide preparations influenced HIV-1 chronically infected cells. Because peptide preparations blocked the HIV-specific DNA synthesis 2 hr after infection without influencing virus adsorption and reverse transcription, we concluded that the block of infection occurred during the penetration of virions through the cell membrane. On the basis of results obtained we propose that our peptide preparations could be used for anti-HIV chemotherapy. The possibility of the existence of receptors for gp41 N-terminal region on target cell membrane is discussed.

Url:
DOI: 10.1006/viro.1993.1260


Affiliations:


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<div type="abstract" xml:lang="en">Abstract: To investigate the mechanism of action of the 22-amino-acid HIV fusion peptide on HIV infection, we studied its influence on virus adsorption and HIV-induced syncytium formation. The effect of the peptide preparations on the synthesis of viral antigens in HIV-infected cell cultures was determined by antigen capture assay, and the inhibition of proviral DNA synthesis was detected by hybridization with a HIV-specific oligonucleotide probe after PCR amplification. Fusion peptides inhibited HIV-induced syncytium formation and antigen production in lyric infected cells, and this effect was increased in conjugation with bovine serum albumin or with synthetic net-charged polymer by its C-terminus. The association of peptide with carrier by N-terminus, or with positive-charged polymer or gelatin completely abolished its effect on HIV infection. No peptide preparations influenced HIV-1 chronically infected cells. Because peptide preparations blocked the HIV-specific DNA synthesis 2 hr after infection without influencing virus adsorption and reverse transcription, we concluded that the block of infection occurred during the penetration of virions through the cell membrane. On the basis of results obtained we propose that our peptide preparations could be used for anti-HIV chemotherapy. The possibility of the existence of receptors for gp41 N-terminal region on target cell membrane is discussed.</div>
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