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Titolo:
A SMALL-MOLECULE INHIBITOR DIRECTED AGAINST THE CHEMOKINE RECEPTOR CXCR4 PREVENTS ITS USE AS AN HIV-1 CORECEPTOR
Autore:
DORANZ BJ; GROVITFERBAS K; SHARRON MP; MAO SH; GOETZ MB; DAAR ES; DOMS RW; OBRIEN WA;
Indirizzi:
UNIV TEXAS,MED BRANCH,DEPT MED,301 UNIV BLVD GALVESTON TX 77555 UNIV TEXAS,MED BRANCH,DEPT MED GALVESTON TX 77555 UNIV PENN,DEPT PATHOL & LAB MED PHILADELPHIA PA 19104 W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED LOS ANGELES CA 90073 UNIV CALIF LOS ANGELES,SCH MED LOS ANGELES CA 00000 CEDARS SINAI MED CTR LOS ANGELES CA 90048
Titolo Testata:
The Journal of experimental medicine
fascicolo: 8, volume: 186, anno: 1997,
pagine: 1395 - 1400
SICI:
0022-1007(1997)186:8<1395:ASIDAT>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTION; ENTRY; INDIVIDUALS; CCR5; GENE; MIP-1-ALPHA; PROGRESSION; LESTR/FUSIN; REPLICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
B.J. Doranz et al., "A SMALL-MOLECULE INHIBITOR DIRECTED AGAINST THE CHEMOKINE RECEPTOR CXCR4 PREVENTS ITS USE AS AN HIV-1 CORECEPTOR", The Journal of experimental medicine, 186(8), 1997, pp. 1395-1400

Abstract

The chemokine receptor CXCR4 is the major coreceptor used for cellular entry by T cell-tropic human immunodeficiency virus (HIV)-1 strains,whereas CCR5 is used by macrophage (M)-tropic strains. Here we show that a small-molecule inhibitor, ALX40-4C, inhibits HIV-1 envelope (Env)-mediated membrane fusion and viral entry directly at the level of coreceptor use. ALX40-4C inhibited HIV-1 use of the coreceptor CXCR4 by T-and dual-tropic HIV-1 strains, whereas use of CCR5 by M-and dual-tropic strains was not inhibited. Dual-tropic viruses capable of using both CXCR4 and CCR5 were inhibited by ALX40-4C only when cells expressedCXCR4 alone. ALX40-4C blocked stromal-derived factor (SDF)-1 alpha-mediated activation of CXCR4 and binding of the monoclonal antibody 12G5to cells expressing CXCR4. Overlap of the ALX40-4C binding site with that of 12G5 and SDF implicates direct blocking of Env interactions, rather than downregulation of receptor, as the mechanism of inhibition. Thus, ALX40-4C represents a small-molecule inhibitor of HIV-1 infection that acts directly against a chemokine receptor at the level of Env-mediated membrane fusion.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 21:55:49