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 gene encoding the coreceptor for macrophage-tropic human immunodeficiency virus type 1 (HIV-1) are resistant to virus infection, and heterozygous 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 CCR5 delta 32/delta 32 donors were resistant to infection with macrophage-tropic HIV-1 and showed slower replication of dual-tropic HIV-1. hu-PBL-SCID mice derived from CCR5 delta 32/+ heterozygotes showed delayed 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.
Picchio
G R
GR
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Gulizia
R J
RJ
Mosier
D E
DE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA; D005838:Genotype; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D012367:RNA, Viral; D019713:Receptors, CCR5; D018121:Receptors, Cytokine / Q000235:genetics* / Q000378:metabolism*; D015728:Receptors, HIV / Q000235:genetics* / Q000378:metabolism*
D016655:HIV Core Protein p24; D012367:RNA, Viral; D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D004247:DNA