Relationship between CCR5((WT/Delta 32)) heterozygosity and HIV-1 reservoir size in adolescents and young adults with perinatally acquired HIV-1 infection
Por:
Martinez-Bonet, M, Gonzalez-Serna, A, Clemente, MI, Moron-Lopez, S, Diaz, L, Navarro, M, Puertas, MC, Leal, M, Ruiz-Mateos, E, Martinez-Picado, J and Munoz-Fernandez, MA
Publicada:
1 may 2017
Resumen:
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/Delta 32)) 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((Delta 32/WT)) genotype and 14 with CCR5((WT/WT)) genotype).
Results: Twenty-three patients were heterozygous for the Delta 32 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((Delta 32/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/Delta 32)) 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/Delta 32)) patients with perinatal HIV infection, which is a characteristic that may affect the design of strategies for reservoir elimination. M. Martinez-Bonet, Clin Microbiol Infect 2017;23:318 (C) 2017 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Filiaciones:
Martinez-Bonet, M:
IiSGM, Hosp Gen Univ Gregorio Maranon, Sect Immunol, Lab Immuno Mol Biol, Madrid, Spain
Spanish HIV HGM BioBank, Madrid, Spain
Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid, Spain
Gonzalez-Serna, A:
IiSGM, Hosp Gen Univ Gregorio Maranon, Sect Immunol, Lab Immuno Mol Biol, Madrid, Spain
Univ Seville, Lab Immunovirol, Clin Unit Infect Dis Microbiol & Prevent Med, Inst Biomed Seville,IBiS,Virgen Rocio Univ Hosp,C, Seville, Spain
Clemente, MI:
IiSGM, Hosp Gen Univ Gregorio Maranon, Sect Immunol, Lab Immuno Mol Biol, Madrid, Spain
Spanish HIV HGM BioBank, Madrid, Spain
Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid, Spain
:
Univ Autonoma Barcelona, AIDS Res Inst IrsiCaixa, Inst Invest Ciencies Salut Germans Trias i Pujol, Badalona, Spain
Diaz, L:
IiSGM, Hosp Gen Univ Gregorio Maranon, Sect Immunol, Lab Immuno Mol Biol, Madrid, Spain
Spanish HIV HGM BioBank, Madrid, Spain
Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid, Spain
Navarro, M:
Hosp Gen Univ Gregorio Maranon, Dept Infect Dis Sect, Paediat Serv, Madrid, Spain
:
Univ Autonoma Barcelona, AIDS Res Inst IrsiCaixa, Inst Invest Ciencies Salut Germans Trias i Pujol, Badalona, Spain
Leal, M:
Univ Seville, Lab Immunovirol, Clin Unit Infect Dis Microbiol & Prevent Med, Inst Biomed Seville,IBiS,Virgen Rocio Univ Hosp,C, Seville, Spain
Ruiz-Mateos, E:
Univ Seville, Lab Immunovirol, Clin Unit Infect Dis Microbiol & Prevent Med, Inst Biomed Seville,IBiS,Virgen Rocio Univ Hosp,C, Seville, Spain
:
Univ Autonoma Barcelona, AIDS Res Inst IrsiCaixa, Inst Invest Ciencies Salut Germans Trias i Pujol, Badalona, Spain
Univ Vic Univ Cent Catalunya UVIC UCC, Barcelona, Spain
ICREA, Barcelona, Spain
Munoz-Fernandez, MA:
IiSGM, Hosp Gen Univ Gregorio Maranon, Sect Immunol, Lab Immuno Mol Biol, Madrid, Spain
Spanish HIV HGM BioBank, Madrid, Spain
Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid, Spain
Green Published, hybrid
|