Relationship between CCR5(Δ32/WT) Heterozygosity and HIV-1 Reservoir Size in Adolescents and Young Adults with Perinatally Acquired HIV-1 Infection

Relationship between CCR5(Δ32/WT) Heterozygosity and HIV-1 Reservoir Size in Adolescents and Young Adults with Perinatally Acquired HIV-1 Infection

Fecha de publicación online: 30/12/2016 Revista: Clinical Microbiology and Infection

Abstract:

Abstract

Jump to SectionIntroductionMethods  Study participants  CCR5 genotyping  Quantification of the proviral HIV-1 DNA  Cellular immunophenotype  Determination of viral tropism  Statistical analysisResults  Cohort characteristics  CCR5(WT/Δ32) heterozygosity association with HIV-1 reservoir size  The association of CCR5(WT/Δ32) heterozygosity with T-cell subsets and cell-associated HIV-1 DNA levels  The relationship between the heterozygous CCR5(WT/Δ32) genotype and viral tropism  CCR5Δ32 heterozygosity association with T-cell activation and immunosenescenceDiscussionAcknowledgementsAppendix A. Supplementary dataTransparency DeclarationReferences

Background

Several host factors contribute to human immunodeficiency virus (HIV) disease progression in the absence of combination antiretroviral therapy (cART). Among them, the CC-chemokine receptor 5 (CCR5) is known to be the main co-receptor used by HIV-1 to enter target cells during the early stages of an HIV-1 infection.

Objective

We evaluated the association of CCR5(WT/Δ32) heterozygosity with HIV-1 reservoir size, lymphocyte differentiation, activation and immunosenescence in adolescents and young adults with perinatally acquired HIV infection receiving cART.

Methods

CCR5 genotype was analysed in 242 patients with vertically transmitted HIV-1 infection from Paediatric Spanish AIDS Research Network Cohort (coRISpe). Proviral HIV-1 DNA was quantified by digital-droplet PCR, and T-cell phenotype was evaluated by flow cytometry in a subset of 24 patients (ten with CCR5(Δ32/WT)genotype and 14 with CCR5(WT/WT) genotype).

Results

Twenty-three patients were heterozygous for the Δ32 genotype but none was homozygous for the mutated CCR5 allele. We observed no difference in the HIV-1 reservoir size (455 and 578 copies of HIV-1 DNA per million CD4+ T cells in individuals with CCR5(WT/WT) and CCR5(Δ32/WT) genotypes, respectively; p 0.75) or in the immune activation markers between both genotype groups. However, we found that total HIV-1 DNA in CD4+ T cells correlated with the percentage of memory CD4+ T cells: a direct correlation in CCR5(WT/Δ32)patients but an inverse correlation in those with the CCR5(WT/WT) genotype.

Conclusions

This finding suggests a differential distribution of the viral reservoir compartment in CCR5(WT/Δ32) patients with perinatal HIV infection, which is a characteristic that may affect the design of strategies for reservoir elimination.

Autores: Martínez-Bonet M, González-Serna A, Clemente MI, Morón-López S, Diaz L, Navarro M, Puertas MC, Leal M, Ruiz-Mateos E, Martinez-Picado J, Muñoz-Fernández MA

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Irsi Caixa

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