Delayed progression to aids by a missense allele of the ccr2...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/12 (2006.01) C07K 14/715 (2006.01) C07K 16/28 (2006.01) C12Q 1/68 (2006.01) C12Q 1/70 (2006.01) G01N 33/53 (2006.01) A61K 38/00 (2006.01) A61K 48/00 (2006.01)

Patent

CA 2300093

The present invention relates to a CCR2 mutant, designated "CCR2-64I". "CCR2- 64I" is a CCR2 gene sequence which has a nucleotide substitution (a G to A substitution) at position 190 (counting from the ATG start codon) such that the valine found position 64 in the wild-type CCR2 amino acid sequence is replaced by an isoleucine. CCR2 is a C-C chemokine receptor and has been implicated as a co-receptor for HIV-1. It has been discovered that the presence of the CCR2-64I allele correlates with a postponement of AIDS outcomes, and that infected individuals who have the CCR2-64I allele are at reduced risk for progression from HIV-1 infection to the development of clinical AIDS and death. Isolated nucleic acid molecule encoding CCR2-64I and the establishment of cell lines that express CCR2-64I provides valuable tools for continuing research on HIV infection. Diagnostic methods for analysis of the allelic frequency of CCR2 wild-type and 64I genes are provided. In addition, antibodies which bind to CCR2-64I, CCR2-64I variants, and CCR2 binding agents represent potential anti-HIV agents.

Cette invention se rapporte à un mutant CCR2, appelé "CCR2-64I". "CCR2-64I" est une séquence de gènes CCR2 qui possède une substitution nucléotidique (substitution G à A) à la position 190 (en comptant à partir du codon de départ ATG), de sorte que la valine située à la position 64 dans la séquence d'acides aminés de type sauvage est remplacée par une isolencine. Le CCR2 est un récepteur de chémokine C-C, impliqué comme co-récepteur pour le VIH-1. On a découvert que la présence de l'allèle CCR2-64I est à mettre en corrélation avec un report de l'évolution en SIDA, et que les sujets infectés ayant l'allèle CCR2-64I présentent moins de risque de voir leur infection à VIH-1 évoluer en SIDA clinique et en mort. Une mollécule d'acide nucléique isolée codant le CCR2-64I et l'établissement de lignées cellulaires qui expriment le CCR2-64I fournissent des outils valables permettant la poursuite des recherches sur les infections à VIH. Des procédés diagnostiques pour l'analyse de la fréquence allélique des gènes 64-I et de type sauvage du CCR2 sont présentés. En outre des anticorps qui se lient au CCR2-64I, des variants de CCR2-64I et des agents de liaison de CCR2 représentent des agents anti-VIH potentiels.

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