CCR5 genotype and resistance to vertical transmission of HIV-1

Sean Philpott, Harold Burger, Tina Charbonneau, Roger Grimson, Sten H. Vermund, Aloise Visosky, Sharon Nachman, Andrea Kovacs, Pamela Tropper, Henry Frey, Barbara Weiser

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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, Δ32, display a high degree of natural resistance to sexual and parenteral transmission of HIV-1. To investigate whether Δ32 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 Δ32 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 Δ32 homozygotes, two uninfected whites (3.77%) and two uninfected Latinos (1.68%). None of the infected children displayed the Δ32 homozygous genotype. Among Latinos and whites, the number of uninfected children who carried the homozygous Δ32 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 Δ32 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.

Original languageEnglish (US)
Pages (from-to)189-193
Number of pages5
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume21
Issue number3
StatePublished - Jul 1 1999
Externally publishedYes

Fingerprint

HIV-1
Genotype
Hispanic Americans
Mothers
HIV Infections
African Americans
CCR5 Receptors
Genes
Zidovudine
Homozygote
Ethnic Groups
Innate Immunity
Gene Frequency
Macrophages
Mutation

Keywords

  • CCR5
  • HIV-1
  • Vertical transmission

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

Cite this

CCR5 genotype and resistance to vertical transmission of HIV-1. / Philpott, Sean; Burger, Harold; Charbonneau, Tina; Grimson, Roger; Vermund, Sten H.; Visosky, Aloise; Nachman, Sharon; Kovacs, Andrea; Tropper, Pamela; Frey, Henry; Weiser, Barbara.

In: Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, Vol. 21, No. 3, 01.07.1999, p. 189-193.

Research output: Contribution to journalArticle

Philpott, S, Burger, H, Charbonneau, T, Grimson, R, Vermund, SH, Visosky, A, Nachman, S, Kovacs, A, Tropper, P, Frey, H & Weiser, B 1999, 'CCR5 genotype and resistance to vertical transmission of HIV-1', Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, vol. 21, no. 3, pp. 189-193.
Philpott S, Burger H, Charbonneau T, Grimson R, Vermund SH, Visosky A et al. CCR5 genotype and resistance to vertical transmission of HIV-1. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology. 1999 Jul 1;21(3):189-193.
Philpott, Sean ; Burger, Harold ; Charbonneau, Tina ; Grimson, Roger ; Vermund, Sten H. ; Visosky, Aloise ; Nachman, Sharon ; Kovacs, Andrea ; Tropper, Pamela ; Frey, Henry ; Weiser, Barbara. / CCR5 genotype and resistance to vertical transmission of HIV-1. In: Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology. 1999 ; Vol. 21, No. 3. pp. 189-193.
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