CHEMOKINE RECEPTOR CCR5 GENOTYPE INFLUENCES THE KINETICS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION IN HUMAN PBL-SCID MICE

Individuals homozygous for a 32-bp deletion (Delta 32) in the CCR5 gen e encoding the coreceptor for macrophage-tropic human immunodeficiency virus type 1 (HIV-1) are resistant to virus infection, and heterozygo us individuals show some slowing of disease progression. The impact of the CCR5 genotype on HIV-1 infection was assessed in vitro and in the human PBL-SCID (hu-PBL-SCID) model. Cells and hu-PBL-SCID mice from C CR5 Delta 32/Delta 32 donors were resistant to infection with macropha ge-tropic HIV-1 and showed slower replication of dual-tropic HIV-1. hu -PBL-SCID mice derived from CCR5 Delta 32/+ heterozygotes showed delay ed replication of macrophage-tropic HIV-1 despite a small and variable effect of heterozygosity on viral replication in vitro, The level of CCR5 expression appears to limit replication of macrophage-tropic and dual-tropic HIV-1 strains in vivo.