Host genetic and immune factors drive evasion of HIV-1 pathogenesis in viremic non-progressors.
CCR5
CTL activation
HIV reservoir
HIV-1 pathogenesis
Translation to patients
VNP
interferon
single-cell RNA sequencing
tryptophan
viremic non-progressor
zonulin
Journal
Med (New York, N.Y.)
ISSN: 2666-6340
Titre abrégé: Med
Pays: United States
ID NLM: 101769215
Informations de publication
Date de publication:
09 Oct 2024
09 Oct 2024
Historique:
received:
13
03
2024
revised:
03
06
2024
accepted:
13
09
2024
medline:
17
10
2024
pubmed:
17
10
2024
entrez:
16
10
2024
Statut:
aheadofprint
Résumé
Viremic non-progressors (VNPs) represent an exceptional and uncommon subset of people with HIV-1, characterized by the remarkable preservation of normal CD4 We implemented a novel single-cell and multiomics approach to comprehensively characterize viral, genomic, transcriptomic, and metabolomic factors driving this exceedingly rare disease phenotype in 16 VNPs and 29 HIV+ progressors. Genetic predisposition to the VNP phenotype was evidenced by a higher prevalence of CCR5Δ32 heterozygosity, which was associated with lower levels of CCR5 expression and a lower frequency of infected cells in peripheral circulation. We also observed reduced levels of plasma markers of intestinal disruption and attenuated interferon responses in VNPs. These factors potentially drive the other phenotypic traits of immune preservation in this population, including the unaltered tryptophan metabolic profile, reduced activation of cytotoxic lymphocytes, and reduced bystander CD4 In summary, our comprehensive analysis identified intricate factors collectively associated with the unique immunovirological equilibrium in VNPs, shedding light on potential avenues for therapeutic exploration in managing HIV pathogenesis. The work was supported by funding from the Spanish Ministry of Science and Innovation and the National Institutes of Health (NIH).
Sections du résumé
BACKGROUND
BACKGROUND
Viremic non-progressors (VNPs) represent an exceptional and uncommon subset of people with HIV-1, characterized by the remarkable preservation of normal CD4
METHODS
METHODS
We implemented a novel single-cell and multiomics approach to comprehensively characterize viral, genomic, transcriptomic, and metabolomic factors driving this exceedingly rare disease phenotype in 16 VNPs and 29 HIV+ progressors.
FINDINGS
RESULTS
Genetic predisposition to the VNP phenotype was evidenced by a higher prevalence of CCR5Δ32 heterozygosity, which was associated with lower levels of CCR5 expression and a lower frequency of infected cells in peripheral circulation. We also observed reduced levels of plasma markers of intestinal disruption and attenuated interferon responses in VNPs. These factors potentially drive the other phenotypic traits of immune preservation in this population, including the unaltered tryptophan metabolic profile, reduced activation of cytotoxic lymphocytes, and reduced bystander CD4
CONCLUSIONS
CONCLUSIONS
In summary, our comprehensive analysis identified intricate factors collectively associated with the unique immunovirological equilibrium in VNPs, shedding light on potential avenues for therapeutic exploration in managing HIV pathogenesis.
FUNDING
BACKGROUND
The work was supported by funding from the Spanish Ministry of Science and Innovation and the National Institutes of Health (NIH).
Identifiants
pubmed: 39413785
pii: S2666-6340(24)00374-X
doi: 10.1016/j.medj.2024.09.007
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests H.H. is co-founder and shareholder of Omniscope, a member of the scientific advisory boards of Nanostring and MiRXES, and consultant to Moderna and Singularity.