Etudes quantitatives et fonctionnelles sur l'incorporation de divers alleles de la molecule HLA-DR de l'hote dans l'enveloppe du VIH-1

Abstract

Nous avons evalue l'incorporation de la proteine HLA-DR (CMH-II) polymorphique cellulaire dans l'enveloppe du VIH-I. A cette fin, nous avons mis au point un systeme de production de stocks viraux ayant incorpore dans leurs enveloppes une des trois molecules a tester, HLA-DR 1, HLA-DR4 et HLA-DRw53. Ces stocks different uniquement par la presence de l'une ou l'autre des molecules mentionnees ci-haut. Premierement, nous avons mesure l'efficacite de l'incorporation des molecules HLA-DR1, HLA-DR4 et HLA-DRw53 dans ce systeme. Suite a cela, nous avons quancifite ces molecules par virus. Enfin, nous avons analyse leurs effets sur la biologie du VIH-1. Nous avons reussi a demontrer que l'infectivite du VIH-1 augmente lorsqu'il y a presence a sa surface d'une des trois molecules provenant des divers alleles du CMH-II. Cependant, une petite variation de l'augmencation d'infectivite est observee dependamment de l'allele en question. Nos experiences ont apporte des renseignements quant a l'importance du polymorphisme du CMH-II dans la pathogenese du VIH-1.

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We assessed the incorporation of the cellular polymorphic HLA-DR (CMH-II) protein into the HIV-I envelope. To this end, we have developed a system for the production of viral stocks having incorporated in their envelopes one of the three molecules to be tested, HLA-DR 1, HLA-DR4 and HLA-DRw53. These stocks differ only by the presence of one or other of the molecules mentioned above. First, we measured the efficiency of the incorporation of HLA-DR1, HLA-DR4 and HLA-DRw53 molecules in this system. Following this, we quantified these molecules by virus. Finally, we analyzed their effects on the biology of HIV-1. We succeeded in demonstrating that the infectivity of HIV-1 increases when there is presence on its surface of one of the three molecules originating from the various alleles of MHC-II. However, a small variation in the increase in infectivity is observed depending on the allele in question. Our experiments have provided insight into the importance of the MHC-II polymorphism in the pathogenesis of HIV-1.