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Titolo:
Multiple nonfunctional alleles of CCR5 are frequent in various human populations
Autore:
Blanpain, C; Lee, B; Tackoen, M; Puffer, B; Boom, A; Libert, F; Sharron, M; Wittamer, V; Vassart, G; Doms, RW; Parmentier, M;
Indirizzi:
Free Univ Brussels, IRIBHN, Lab Histol Neuroanat & Neuropathol, B-1070 Brussels, Belgium Free Univ Brussels Brussels Belgium B-1070 hol, B-1070 Brussels, Belgium Free Univ Brussels, Serv Genet Med, B-1070 Brussels, Belgium Free Univ Brussels Brussels Belgium B-1070 Med, B-1070 Brussels, Belgium Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 & Lab Med, Philadelphia, PA 19104 USA
Titolo Testata:
BLOOD
fascicolo: 5, volume: 96, anno: 2000,
pagine: 1638 - 1645
SICI:
0006-4971(20000901)96:5<1638:MNAOCA>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; CHEMOKINE-RECEPTOR GENE; AMINO-TERMINAL DOMAIN; CD8(+) T-CELLS; HIV-1 INFECTION; SIGNAL-TRANSDUCTION; DISEASE PROGRESSION; GP120 BINDING; DELTA-CCR5 MUTATION; CORECEPTOR FUNCTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Parmentier, M Free Univ Brussels, IRIBHN, Lab Histol Neuroanat & Neuropathol, ULB CampusErasme,808 Route Lennik, B-1070 Brussels, Belgium Free Univ Brussels ULB Campus Erasme,808 Route Lennik Brussels Belgium B-1070
Citazione:
C. Blanpain et al., "Multiple nonfunctional alleles of CCR5 are frequent in various human populations", BLOOD, 96(5), 2000, pp. 1638-1645

Abstract

CCR5 is the major coreceptor for macrophage-tropic strains of the human immunodeficiency virus type I(HIV-1), Homozygotes for a 32-base pair (bp) deletion in the coding sequence of the receptor (CCR5 Delta 32) were found to be highly resistant to viral infection, and CCR5 became, therefore, one of the paradigms illustrating the influence of genetic variability onto individual susceptibility to infectious and other diseases. We investigated the functional consequences of 16 other natural CCR5 mutations described in various human populations. We found that 10 of these variants are efficiently expressed at the cell surface, bind [I-125]-MIP-1 beta with affinities similar to wtCCR5, respond functionally to chemokines, and act as HIV-1 coreceptors. In addition to Delta 32, six mutations were characterized by major alterations in their functional response to chemokines, as a consequence of intracellular trapping and poor expression at the cell surface (C101X, FS299), general or specific alteration of ligand binding affinities (C20S, C178R,A29S), or relative inability to mediate receptor activation (L55Q), A29S displayed an unusual pharmacological profile, binding and responding to MCP-2 similarly to wtCCR5, but exhibiting severely impaired binding and functional responses to MIP-1 alpha, MIP-1 beta, and RANTES, In addition to Delta 32, only C101X was totally unable to mediate entry of HIV-1. The fact that nonfunctional CCR5 alleles are relatively frequent in various human populations reinforces the hypothesis of a selective pressure favoring these alleles, (C) 2000 by The American Society of Hematology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 13:01:28