There are differences in the susceptibility of humans to HIV-1. This genetic variability can be analysed by using a range of approaches - analysis of candidate genes, genome scans and genome-wide association analysis, and by analysis of signatures of selective pressure exerted by retroviruses and retroelements on the primate genome.This proposal implements a number of tools and develops dedicated biological systems to address these questions:1.Development of a standardized in vitro system where immortalized B lymphocytes from multigeneration families are transduced by HIV-based lentiviruses. The family structure allows genome scans to map loci associated with cellular susceptibility to HIV-1.2.Genome-wide association analyses on infected individuals. For this, DNA is genotype using Illumina technology: >500.000 SNPs per individual.3.Analysis of evolutionary pressures on genes involved in HIV pathogenesis. This approach allows also the reconstruction of ancestral proteins, thus assessing the steps leading to modern protein specificities.