CCR5 genotype and resistance to vertical transmission of HIV-1.
A human gene has been identified that affects susceptibility to HIV-1 infection. The gene codes for CCR5, the coreceptor for macrophage-tropic strains of HIV-1. Individuals who are homozygous for a deleted, mutant form of the gene, delta32, display a high degree of natural resistance to sexual and parenteral transmission of HIV-1. To investigate whether delta32 plays a role in vertical transmission, we determined the CCR5 genotype of 552 children born to infected mothers in the United States and correlated the genotypes with HIV-1 infection status. Of these children, 13% were white, 30% Latino, and 56% African American, reflecting the ethnic makeup of infected women in the United States. The delta32 gene frequency varied among these groups, ranging from 0.08 in whites to 0.02 in both Latinos and African Americans. Approximately 27% of the children in each ethnic group were infected. Four children were identified as delta32 homozygotes, two uninfected whites (3.77%) and two uninfected Latinos (1.68%). None of the infected children displayed the delta32 homozygous genotype. Among Latinos and whites, the number of uninfected children who carried the homozygous delta32 mutation was significantly greater than that predicted by the Hardy-Weinberg equilibrium (p < .001 for Latinos, p = .044 for whites). This association was noted in Latino and white children whose mothers were either treated or untreated with zidovudine. These data document the occurrence of the homozygous delta32 genotype among children of HIV-1-infected mothers and suggest that this mutant genotype may confer protection from mother-to-child transmission of HIV-1. They also suggest that sexual, parenteral, and vertical transmission all involve processes that use CCR5 as a coreceptor for primary HIV-1 infection. Therefore, blocking the CCR5 receptor may provide an additional strategy to prevent HIV-1 vertical transmission.
Philpott
S
S
Wadsworth Center, New York State Department of Health, Albany 12208-2022, USA.
Burger
H
H
Charbonneau
T
T
Grimson
R
R
Vermund
S H
SH
Visosky
A
A
Nachman
S
S
Kovacs
A
A
Tropper
P
P
Frey
H
H
Weiser
B
B
D000483:Alleles; D019380:Anti-HIV Agents / Q000627:therapeutic use; D002648:Child; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000635:transmission; D015497:HIV-1; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D018445:Infectious Disease Transmission, Vertical; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000145:classification / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D019713:Receptors, CCR5; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine