title: Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection.
abstract: Rare individuals have been multiply exposed to HIV-1 but remain uninfected. The CD4+ T-cells of two of these individuals, designated EU2 and EU3, are highly resistant in vitro to the entry of primary macrophagetropic virus but are readily infectable with transformed T-cell line adapted viruses. We report here on the genetic basis of this resistance. We found that EU2 and EU3 have a homozygous defect in CKR-5, the gene encoding the recently described coreceptor for primary HIV-1 isolates. These individuals appear to have inherited a defective CKR-5 allele that contains an internal 32 base pair deletion. The encoded protein is severely truncated and cannot be detected at the cell surface. Surprisingly, this defect has no obvious phenotype in the affected individuals. Thus, a CKR-5 allele present in the human population appears to protect homozygous individuals from sexual transmission of HIV-1. Heterozygous individuals are quite common (approximately 20%) in some populations. These findings indicate the importance of CKR-5 in HIV-1 transmission and suggest that targeting the HIV-1-CKR-5 interaction may provide a means of preventing or slowing disease progression.
authors: Aaron Diamond AIDS Research Center, Rockefeller University New York, New York 10016, USA.
authors: R
authors: R
authors: Liu
authors: W A
authors: WA
authors: Paxton
authors: S
authors: S
authors: Choe
authors: D
authors: D
authors: Ceradini
authors: S R
authors: SR
authors: Martin
authors: R
authors: R
authors: Horuk
authors: M E
authors: ME
authors: MacDonald
authors: H
authors: H
authors: Stuhlmann
authors: R A
authors: RA
authors: Koup
authors: N R
authors: NR
authors: Landau
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary / Q000032:analysis; D004279:DNA, Viral; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006720:Homozygote; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008969:Molecular Sequence Data; D019713:Receptors, CCR5; D018121:Receptors, Cytokine / Q000235:genetics*; D015728:Receptors, HIV / Q000235:genetics*; D015183:Restriction Mapping; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D018076:DNA, Complementary; D004279:DNA, Viral; D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D015728:Receptors, HIV