Homozygous delta 32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient

AIDS. 1997 Aug;11(10):F67-71. doi: 10.1097/00002030-199710000-00001.

Abstract

Background: Recent research has found that entry of non-syncytium-inducing (NSI), monocyte-macrophage-tropic HIV-1 isolates requires binding to both CD4 and CCR5 receptors, and that delta 32/delta 32 homozygous individuals are protected against infection.

Objective: To analyse the polymorphism of CCR-5 gene in HIV-1-infected and uninfected subjects.

Design and methods: CCR-5 sequences were amplified by polymerase chain reaction (PCR) from DNA of peripheral blood mononuclear cells. Samples from 152 HIV-1-infected subjects and 122 uninfected controls were tested for the detection of the 32 base-pair deletion. HIV-1 phenotype was determined by viral isolation and MT-2 evaluation.

Results: The wild-type/delta 32 heterozygous and delta 32/delta 32 homozygous conditions were represented in 10.7 and 0.8% of healthy controls and in 9.8 and 0.7% of HIV-1-infected subjects, respectively. Of note, the delta 32/delta 32 deletion of the CCR-5 gene was detected by PCR and sequencing confirmed in a patient with progressive infection harbouring a clade B virus with SI phenotype.

Conclusions: delta 32/delta 32 homozygosity for the CCR-5 gene does not confer absolute protection against HIV-1 infection, suggesting that either macrophage-tropic viral strains could use coreceptors other than CCR-5 or infect independently of the presence of a functional CCR-5 coreceptor. Alternatively, primary infection sustained by T-cell-tropic isolates, although exceptional, may occur.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cloning, Molecular
  • Cohort Studies
  • HIV Envelope Protein gp120 / genetics
  • HIV Seropositivity / epidemiology
  • HIV Seropositivity / genetics*
  • HIV-1 / classification
  • HIV-1 / pathogenicity*
  • Heterozygote
  • Humans
  • Immunity, Innate / genetics
  • Italy / epidemiology
  • Male
  • Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Receptors, CCR5
  • Receptors, Cytokine / genetics*
  • Receptors, HIV / genetics*
  • Risk Factors
  • Sequence Analysis, DNA
  • Sequence Deletion
  • Viremia / diagnosis
  • White People / genetics

Substances

  • HIV Envelope Protein gp120
  • Receptors, CCR5
  • Receptors, Cytokine
  • Receptors, HIV