Decreased susceptibility of peripheral blood mononuclear cells from individuals heterozygous for a mutant CCR5 allele to HIV infection

Ana Kim, Massimo Pettoello-Mantovani, Harris Goldstein

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective: Individuals homozygous for a deletion in the CCR5 gene (CCR5Δ32/CCR5Δ32) are resistant to HIV infection, indicating that this particular chemokine receptor plays a crucial role in the initiation of in vivo HIV infection. We investigated the effect of the heterozygote genotype (CCR5/CCR5Δ32) on susceptibility of peripheral blood mononuclear cells (PBMC) to HIV infection. Design: Sensitivity to HIV infection of PBMC from volunteers with either the CCR5/CCR5, CCR5/CCR5Δ32, or CCR5Δ32/CCR5Δ32 genotypes was examined by challenging their PBMCs with serial titers of HIV isolates with different cellular tropisms. The genotype of the PBMCs was correlated with the lowest viral inoculum required to initiate productive infection with either three M-tropic HIV-1 isolates, (92RW009A, HIV-1(ada), and HIV-159), one dual-tropic HIV-1 isolate (92BR021), or two T-tropic HIV- 1 isolates (92UG021 and 92UG029). Results: PBMCs from the CCR5/CCR5Δ32 group required a significantly higher inoculum (p value from .036 to .003) to become infected with these three M-tropic HIV-1 isolates than did PBMC from the CCR5/CCR5 group, but became infected after exposure to an inoculum of T- tropic HIV-1 isolates that was comparable to that which infected PBMCs from the CCR5/CCR5 individuals. Conclusions: The decreased susceptibility of PBMCs from individuals heterozygous for the CCR5 deletion to HIV infection by M- tropic HIV-1 isolates may provide a mechanistic explanation for the delayed progression of disease in some CCR5/CCR5Δ32 individuals.

Original languageEnglish (US)
Pages (from-to)145-149
Number of pages5
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume19
Issue number2
StatePublished - Oct 1 1998

Fingerprint

HIV Infections
HIV-1
Blood Cells
Alleles
Genotype
HIV
Tropism
Chemokine Receptors
Heterozygote
Disease Progression
Volunteers
Infection
Genes

Keywords

  • CCR5
  • HIV
  • Macrophage-tropic
  • Nonsyncytium-inducing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

Cite this

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title = "Decreased susceptibility of peripheral blood mononuclear cells from individuals heterozygous for a mutant CCR5 allele to HIV infection",
abstract = "Objective: Individuals homozygous for a deletion in the CCR5 gene (CCR5Δ32/CCR5Δ32) are resistant to HIV infection, indicating that this particular chemokine receptor plays a crucial role in the initiation of in vivo HIV infection. We investigated the effect of the heterozygote genotype (CCR5/CCR5Δ32) on susceptibility of peripheral blood mononuclear cells (PBMC) to HIV infection. Design: Sensitivity to HIV infection of PBMC from volunteers with either the CCR5/CCR5, CCR5/CCR5Δ32, or CCR5Δ32/CCR5Δ32 genotypes was examined by challenging their PBMCs with serial titers of HIV isolates with different cellular tropisms. The genotype of the PBMCs was correlated with the lowest viral inoculum required to initiate productive infection with either three M-tropic HIV-1 isolates, (92RW009A, HIV-1(ada), and HIV-159), one dual-tropic HIV-1 isolate (92BR021), or two T-tropic HIV- 1 isolates (92UG021 and 92UG029). Results: PBMCs from the CCR5/CCR5Δ32 group required a significantly higher inoculum (p value from .036 to .003) to become infected with these three M-tropic HIV-1 isolates than did PBMC from the CCR5/CCR5 group, but became infected after exposure to an inoculum of T- tropic HIV-1 isolates that was comparable to that which infected PBMCs from the CCR5/CCR5 individuals. Conclusions: The decreased susceptibility of PBMCs from individuals heterozygous for the CCR5 deletion to HIV infection by M- tropic HIV-1 isolates may provide a mechanistic explanation for the delayed progression of disease in some CCR5/CCR5Δ32 individuals.",
keywords = "CCR5, HIV, Macrophage-tropic, Nonsyncytium-inducing",
author = "Ana Kim and Massimo Pettoello-Mantovani and Harris Goldstein",
year = "1998",
month = "10",
day = "1",
language = "English (US)",
volume = "19",
pages = "145--149",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
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TY - JOUR

T1 - Decreased susceptibility of peripheral blood mononuclear cells from individuals heterozygous for a mutant CCR5 allele to HIV infection

AU - Kim, Ana

AU - Pettoello-Mantovani, Massimo

AU - Goldstein, Harris

PY - 1998/10/1

Y1 - 1998/10/1

N2 - Objective: Individuals homozygous for a deletion in the CCR5 gene (CCR5Δ32/CCR5Δ32) are resistant to HIV infection, indicating that this particular chemokine receptor plays a crucial role in the initiation of in vivo HIV infection. We investigated the effect of the heterozygote genotype (CCR5/CCR5Δ32) on susceptibility of peripheral blood mononuclear cells (PBMC) to HIV infection. Design: Sensitivity to HIV infection of PBMC from volunteers with either the CCR5/CCR5, CCR5/CCR5Δ32, or CCR5Δ32/CCR5Δ32 genotypes was examined by challenging their PBMCs with serial titers of HIV isolates with different cellular tropisms. The genotype of the PBMCs was correlated with the lowest viral inoculum required to initiate productive infection with either three M-tropic HIV-1 isolates, (92RW009A, HIV-1(ada), and HIV-159), one dual-tropic HIV-1 isolate (92BR021), or two T-tropic HIV- 1 isolates (92UG021 and 92UG029). Results: PBMCs from the CCR5/CCR5Δ32 group required a significantly higher inoculum (p value from .036 to .003) to become infected with these three M-tropic HIV-1 isolates than did PBMC from the CCR5/CCR5 group, but became infected after exposure to an inoculum of T- tropic HIV-1 isolates that was comparable to that which infected PBMCs from the CCR5/CCR5 individuals. Conclusions: The decreased susceptibility of PBMCs from individuals heterozygous for the CCR5 deletion to HIV infection by M- tropic HIV-1 isolates may provide a mechanistic explanation for the delayed progression of disease in some CCR5/CCR5Δ32 individuals.

AB - Objective: Individuals homozygous for a deletion in the CCR5 gene (CCR5Δ32/CCR5Δ32) are resistant to HIV infection, indicating that this particular chemokine receptor plays a crucial role in the initiation of in vivo HIV infection. We investigated the effect of the heterozygote genotype (CCR5/CCR5Δ32) on susceptibility of peripheral blood mononuclear cells (PBMC) to HIV infection. Design: Sensitivity to HIV infection of PBMC from volunteers with either the CCR5/CCR5, CCR5/CCR5Δ32, or CCR5Δ32/CCR5Δ32 genotypes was examined by challenging their PBMCs with serial titers of HIV isolates with different cellular tropisms. The genotype of the PBMCs was correlated with the lowest viral inoculum required to initiate productive infection with either three M-tropic HIV-1 isolates, (92RW009A, HIV-1(ada), and HIV-159), one dual-tropic HIV-1 isolate (92BR021), or two T-tropic HIV- 1 isolates (92UG021 and 92UG029). Results: PBMCs from the CCR5/CCR5Δ32 group required a significantly higher inoculum (p value from .036 to .003) to become infected with these three M-tropic HIV-1 isolates than did PBMC from the CCR5/CCR5 group, but became infected after exposure to an inoculum of T- tropic HIV-1 isolates that was comparable to that which infected PBMCs from the CCR5/CCR5 individuals. Conclusions: The decreased susceptibility of PBMCs from individuals heterozygous for the CCR5 deletion to HIV infection by M- tropic HIV-1 isolates may provide a mechanistic explanation for the delayed progression of disease in some CCR5/CCR5Δ32 individuals.

KW - CCR5

KW - HIV

KW - Macrophage-tropic

KW - Nonsyncytium-inducing

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JF - Journal of Acquired Immune Deficiency Syndromes

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