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Oligodeossinucleotidi nativi selettivamente attivi in vitro contro il virus dell'immunodeficienza umana di tipo 1: ruolo del G-quartet

Pani, Alessandra - Loddo, Roberta - Murgioni, Chiara - Marongiu, Esther - La Colla, Paolo - Marongiu, M. Elena (2000) Oligodeossinucleotidi nativi selettivamente attivi in vitro contro il virus dell'immunodeficienza umana di tipo 1: ruolo del G-quartet. Rendiconti del Seminario della Facoltà di Scienze dell'Università di Cagliari, 70 (Supple). pp. 36-48. ISSN 0370727X

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Abstract

Among a series of unmodified phosphodiester (PO)-oligodeoxynucleotides (PO-ODNs) complementary to some of human immunodeficiency virus type 1 (HIV-1) regulatory genes, several PO-ODN sequences complementary to the vpr gene (POODNs-α-vpr, where a-vpr is the antisense vpr sequence) emerged as potent inhibitors(at concentration of 0,8 to 3,3 μM) of HIV-1 multiplication in de novo infected MT-4 cells, while they showed no cytoxicity for uninfected cells at concentration up to 100 μM. Unlike phosphorothioate counterparts, PO-ODN-α-vpr sequences were not inhibitory to HIV-2 multiplication in de novo infected C8166 cells and neither prevented the fusion between chronically infected and bystander CD4+ cells nor inhibited the activity of the HIV-1 reverse transcriptase in enzyme assays. Moreover, they were not inhibitory to HIV-1 multiplication in chronically infected cells. Delayed addition experiments showed that PO-ODNs-α-vpr inhibit an event in the HIV-1 replication cycle following adsorption to the host cell, but preceeding reverse transcription. Structure-activity relationship studies indicated that antiviral activity of the test PO-ODN-α-vpr sequences is not related to the antisense mechanism but to the presence, within the active sequences, of contiguous guanine residues. Physical characterization of the test POODNs suggested that the active structure is a tetramer stabilized by G quartets (i.e., four G residues connected by eight hydrogen bonds).

Item Type:Article
Date:2000
Institution:Università degli Studi di Cagliari
Divisions:Centri > Seminario Scientifico della Facolta' di Scienze MM.FF.NN.
Subjects:Area 05 - Scienze biologiche > BIO/19 Microbiologia generale
Uncontrolled Keywords:(PO)-oligodeoxynucleotides, HIV-1, vpr gene, HIV-2, C8166 cells
ID Code:301
Deposited On:12 Nov 2008 11:06

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