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Titolo:
ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACTIVITY OF AN OLIGOCATIONICCOMPOUND MEDIATED VIA GP120 V3 INTERACTIONS
Autore:
OBRIEN WA; SUMNERSMITH M; MAO SH; SADEGHI S; ZHAO JQ; CHEN IY;
Indirizzi:
W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,11301 WILSHIRE BLVD LOS ANGELES CA 90073 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED LOS ANGELES CA 90024 UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL LOS ANGELES CA 90024 ALLELIX BIOPHARMACEUT INC MISSISSAUGA ON CANADA
Titolo Testata:
Journal of virology
fascicolo: 5, volume: 70, anno: 1996,
pagine: 2825 - 2831
SICI:
0022-538X(1996)70:5<2825:ATAOAO>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
SYNCYTIUM-INDUCING PHENOTYPE; RECOMBINANT SOLUBLE CD4; LONG TERMINAL REPEAT; ENVELOPE GLYCOPROTEIN; SULFATED POLYSACCHARIDES; DEXTRAN SULFATE; TRANS-ACTIVATION; GENE-EXPRESSION; BINDING-SITE; CELL TROPISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
67
Recensione:
Indirizzi per estratti:
Citazione:
W.A. Obrien et al., "ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACTIVITY OF AN OLIGOCATIONICCOMPOUND MEDIATED VIA GP120 V3 INTERACTIONS", Journal of virology, 70(5), 1996, pp. 2825-2831

Abstract

An oligocationic peptide compound (ALX40-4C) was developed for consideration in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. This compound was designed to mimic the basic domain of the HIV-1 transactivation protein, Tat, and will competitively,inhibit Tat binding to its specific RNA hairpin target (TAR [transactivation region]), found at the 5' end of all HIV-1 transcripts. Blocking Tat-TAR interactions can abrogate HIV-1 replication. ALX40-4C was shown to inhibit replication of HIV-1(NL4-3) in a range of cell types, includingprimary cells and transformed cell lines, by as much as 10(4)-fold. In some experiments, virus rescue was not possible even after removal of ALX40-4C from the cultures. Strain-dependent resistance has been demonstrated for all antiretroviral agents tested; therefore, we tested for variable sensitivity to ALX40-4C. The cloned primary strains, HIV-1(JR-CSF) and HIV-1(JR-FL,) ALX40-4C inhibition. Unexpectedly, determinants for efficient ALX40-4C inhibition were mapped by using recombinant virus strains to the V3 region of gp120 and were shown to act at early events in viral replication, which include viral entry. If entry and reverse transcription are bypassed by transfection, a more modest, virus strain-independent inhibition is shown; this inhibition is likelydue to blocking of Tat-TAR interaction. 'Thus, the highly basic oligocationic Tat inhibitor ALX40-4C appears to interfere with initial virus-target cell interactions which involve HIV-1 gp120 V3 determinants, most efficiently for T-cell line-adapted strains.

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Documento generato il 29/11/20 alle ore 00:40:14