A purified polypeptide, isolated nucleic acids encoding said...

C - Chemistry – Metallurgy – 07 – K

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C07K 14/15 (2006.01) C12N 15/867 (2006.01)

Patent

CA 2524892

The present invention relates to a purified polypeptide, which is capable of mediating infection of a cell, by use of the polytropic/xenotropic receptor encoded by the Rmc1 locus from a NIH Swiss inbred NFS/N mouse for entry, and unable of mediating infection of a cell by use of a human polytropic/xenotropic receptor encoded by the human RMC1 locus. The present invention especially relates to an envelope protein from the Murine Leukaemia Virus (MLV) strain SL3-2, which is capable of infecting murine cells through usega of the polytropic receptor encoded by the Rmc1 locus, but lacks the ability of infecting human cells expressing the corresponding xenotropic receptor encoded by the RMC1 locus. The present invention furthermore demonstrate that replacements of at least one specified amino acid in the polypeptide can alter the tropism and enable the SL3-2 envelope to infect a human cell by use of the human polytropic/xenotropic receptor encoded by the RMC1 locus for entry.

L'invention concerne un polypeptide purifié assurant la médiation de l'infection d'une cellule, au moyen du récepteur polytropique/xénotropique codé par le locus Rmc1 d'une souris NFS/N NIH Swiss de type pur pour l'entrée, et n'assurant pas la médiation de l'infection d'une cellule au moyen d'un récepteur polytropique/xénotropique codé par le locus RMC1. L'invention concerne en particulier une protéine enveloppe de souche SL3-2 du virus de la leucémie murine assurant l'infection de cellules murines au moyen du récepteur polytropique codé par le locus Rmc1 mais n'assurant pas l'infection de cellules humaines qui expriment le récepteur polytropique correspondant codé par le locus RMC1. L'invention concerne aussi la possibilité pour des remplacements d'au moins un acide aminé spécifié dans le polypeptide de modifier le tropisme et de permettre à l'enveloppe SL3-2 d'infecter une cellule humaine au moyen du récepteur polytropique/xénotropique humain codé par le locus RMC1 pour l'entrée.

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