Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound.

Adaptor Proteins, Signal Transducing / genetics Anti-HIV Agents / therapeutic use Apoptosis Regulatory Proteins / genetics CD4-Positive T-Lymphocytes / metabolism Cytokines / genetics Female HIV Infections / drug therapy HIV-1 / drug effects Humans Male Transcription Factors / genetics Tripartite Motif Proteins / genetics Ubiquitin Thiolesterase / genetics Ubiquitin-Protein Ligases / genetics Ubiquitins / genetics Withholding Treatment

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
10 01 2022
Historique:
received: 15 07 2021
accepted: 08 12 2021
entrez: 11 1 2022
pubmed: 12 1 2022
medline: 3 3 2022
Statut: epublish

Résumé

Although certain individuals with HIV infection can stop antiretroviral therapy (ART) without viral load rebound, the mechanisms under-pinning 'post-treatment control' remain unclear. Using RNA-Seq we explored CD4 T cell gene expression to identify evidence of a mechanism that might underpin virological rebound and lead to discovery of associated biomarkers. Fourteen female participants who received 12 months of ART starting from primary HIV infection were sampled at the time of stopping therapy. Two analysis methods (Differential Gene Expression with Gene Set Enrichment Analysis, and Weighted Gene Co-expression Network Analysis) were employed to interrogate CD4+ T cell gene expression data and study pathways enriched in post-treatment controllers versus early rebounders. Using independent analysis tools, expression of genes associated with type I interferon responses were associated with a delayed time to viral rebound following treatment interruption (TI). Expression of four genes identified by Cox-Lasso (ISG15, XAF1, TRIM25 and USP18) was converted to a Risk Score, which associated with rebound (p < 0.01). These data link transcriptomic signatures associated with innate immunity with control following stopping ART. The results from this small sample need to be confirmed in larger trials, but could help define strategies for new therapies and identify new biomarkers for remission.

Identifiants

DOI: 10.1038/s41598-021-04212-9 PMID: 35013427 PMC: PMC8748440
pubmed: 35013427
doi: 10.1038/s41598-021-04212-9
pii: 10.1038/s41598-021-04212-9
pmc: PMC8748440
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
Anti-HIV Agents 0
Apoptosis Regulatory Proteins 0
Cytokines 0
Transcription Factors 0
Tripartite Motif Proteins 0
Ubiquitins 0
XAF1 protein, human 0
ISG15 protein, human 60267-61-0
TRIM25 protein, human EC 2.3.2.27
Ubiquitin-Protein Ligases EC 2.3.2.27
USP18 protein, human EC 3.4.19.12
Ubiquitin Thiolesterase EC 3.4.19.12

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

462

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI133673
Pays : United States
Organisme : Medical Research Council
ID : MR/L006588/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P011233/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L00528X/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 069598/Z/02/Z
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

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Auteurs

P Zacharopoulou (P)

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

E Marchi (E)

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

A Ogbe (A)

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

N Robinson (N)

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

H Brown (H)

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

M Jones (M)

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

L Parolini (L)

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

M Pace (M)

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

N Grayson (N)

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Department of Paediatrics, University of Oxford, Oxford, UK.

P Kaleebu (P)

Medical Research Council/Uganda Virus Research Institute, Entebbe, Uganda.

H Rees (H)

Wits Reproductive Health and HIV Institute of the University of the Witwatersrand in Johannesburg, Johannesburg, South Africa.

S Fidler (S)

Division of Medicine, Wright Fleming Institute, Imperial College, London, UK.
Imperial College NIHR Biomedical Research Centre, London, UK.

P Goulder (P)

Department of Paediatrics, University of Oxford, Oxford, UK.

P Klenerman (P)

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
National Institute of Health Research Biomedical Research Centre, Oxford, UK.

J Frater (J)

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK. john.frater@ndm.ox.ac.uk.
National Institute of Health Research Biomedical Research Centre, Oxford, UK. john.frater@ndm.ox.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Expression of type I interferon-associated...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiviraux › Antirétroviraux › Agents antiVIH › Expression of type I interferon-associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines régulatrices de l'apoptose › Expression of type I interferon-associated...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD4+ › Expression of type I interferon-associated...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Expression of type I interferon-associated...
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Infections à VIH › Expression of type I interferon-associated...
questionsmedicales.fr › Virus › Virus à ARN › Retroviridae › Lentivirus › Lentivirus des primates › VIH (Virus de l'Immunodéficience Humaine) › VIH-1 (Virus de l'Immunodéficience Humaine de type 1) › Expression of type I interferon-associated...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Expression of type I interferon-associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Expression of type I interferon-associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines à motif tripartite › Expression of type I interferon-associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées à la maladie de Parkinson › Ubiquitin thiolesterase › Expression of type I interferon-associated...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › Expression of type I interferon-associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Ubiquitines › Expression of type I interferon-associated...
questionsmedicales.fr › Établissements, main d'oeuvre et services de soins de santé › Services de santé › Soins aux patients › Abstention thérapeutique › Expression of type I interferon-associated...