Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Evidence for common structural determinants of human immunodeficiency virus type 1 coreceptor activity provided through functional analysis of CCR5/CXCR4 chimeric coreceptors
Autore:
Pontow, S; Ratner, L;
Indirizzi:
Washington Univ, Sch Med, Dept Internal Med, Div Mol Oncol, St Louis, MO 63110 USA Washington Univ St Louis MO USA 63110 v Mol Oncol, St Louis, MO 63110 USA
Titolo Testata:
JOURNAL OF VIROLOGY
fascicolo: 23, volume: 75, anno: 2001,
pagine: 11503 - 11514
SICI:
0022-538X(200112)75:23<11503:EFCSDO>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMINO-TERMINAL DOMAIN; CHEMOKINE RECEPTOR CCR5; 2ND EXTRACELLULAR LOOP; HIV-1 MEMBRANE-FUSION; GP120 BINDING; ENVELOPE GLYCOPROTEIN; HIGHLY POTENT; DISTINCT CCR5; CXCR4 DOMAINS; VIRAL ENTRY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Ratner, L Washington Univ, Sch Med, Dept Internal Med, Div Mol Oncol, 660 S Euclid,Campus Box 8069, St Louis, MO 63110 USA Washington Univ 660 S Euclid,Campus Box 8069 St Louis MO USA 63110
Citazione:
S. Pontow e L. Ratner, "Evidence for common structural determinants of human immunodeficiency virus type 1 coreceptor activity provided through functional analysis of CCR5/CXCR4 chimeric coreceptors", J VIROLOGY, 75(23), 2001, pp. 11503-11514

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection in vivo is dependentupon the interaction of the viral envelope glycoprotein gp120 with CC chemokine receptor 5 (CCR5) or CXC chemokine receptor 4 (CXCR4). To study the determinants of the gp120-coreceptor association, we generated a set of chimeric HIV-1 coreceptors which express all possible combinations of the four extracellular domains of CCR5 and CXCR4. Stable U87 astroglioma cell lines expressing CD4 and individual chimeric coreceptor proteins were tested against a variety of R5, X4, and R5X4 envelope glycoproteins and virus strains for their ability to support HIV-1-mediated cell fusion and infection, respectively. Each of the cell lines promoted fusion with cells expressing an HIV envelope glycoprotein, except for U87.CD4.5455, which presents the firstextracellular loop (ECL1) and flanking sequences of CXCR4 in the context of CCR5. However, all of the chimeric coreceptors allowed productive infection by one or more of the viral strains tested. Viral phenotype was a predictive factor for the observed activity of the chimeric molecules; X4 and R5X4 HIV strains utilized a majority of the chimeras, while R5 strains were limited in their ability to infect cells expressing these chimeric molecules. The expression of CCR5 ECL2 within the CXCR4 backbone supported infection by an R5 primary isolate, but no chimeras bearing the N terminus of CCR5 exhibited activity with R5 strains. Remarkably, the introduction of any CXCR4domain into the CCR5 backbone was sufficient to allow utilization by multiple X4 strains. However, critical determinants within ECL2 and/or ECL3 of CXCR4 were apparent for all X4 viruses upon replacement of these domains in CXCR4 with CCR5 sequences. Unexpectedly, chimeric coreceptor-facilitated entry was blocked in all cases by the presence of the CXCR4-specific inhibitor AMD3100. Our data provide proof that CCR5 contains elements that support usage by X4 viral strains and demonstrate that the gp120 interaction sites of CCR5 and CXCR4 are structurally related.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 13:37:34