DataVXAdvanced SciencePaper
journal article·2025-04Open access

Host Plasma Microenvironment in Immunometabolically Impaired HIV Infection Leads to Dysregulated Monocyte Function and Synaptic Transmission Ex Vivo

Flora Mikaeloff, Marco Gelpi, Alejandra Escós, Tianqi Wang, Soham Gupta, Anna Olofsson, Sara Svensson Akusjärvi, Sabrina Schuster, Prajakta Naval, Vikas Sood, Negin Nikouyan, Andreas D. Knudsen, Beate Vestad, Julie Høgh, Johannes R. Hov, Thomas Benfield, Marius Trøseid, Vinay Pawar, Marijana Rucevic, Rui Benfeitas, Ákos Végvári, Liam O'Mahony, Rajkumar Savai, Niklas K. Björkström, Magda Lourda, João Pedro de Magalhães, Siegfried Weiss, Adil Mardinoglu, Mukesh Kumar Varshney, Annika C. Karlsson, Yasir Ahmed Syed, Susanne D. Nielsen, Ujjwal Neogi

Advanced Science· Volume 12· Issue 16
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Source abstract

Abstract

Abstract Risk stratification using multi‐omics data deepens understanding of immunometabolism in successfully treated people with HIV (PWH) is inadequately explained. A personalized medicine approach integrating blood cell transcriptomics, plasma proteomics, and metabolomics is employed to identify the mechanisms of immunometabolic complications in prolonged treated PWH from the COCOMO cohort. Among the PWHs, 44% of PWH are at risk of experiencing immunometabolic complications identified using the network‐based patient stratification method. Utilizing advanced machine learning techniques and a Bayesian classifier, five plasma protein biomarkers; Tubulin Folding Cofactor B (TBCB), Gamma‐Glutamylcyclotransferase (GGCT), Taxilin Alpha (TXLNA), Pyridoxal Phosphate Binding Protein (PLPBP) and Large Tumor Suppressor Kinase 1 (LATS1) are identified as highly differentially abundant between healthy control (HC)‐like and immunometabolically at‐risk PWHs (all FDR<10−10). The personalized metabolic models predict metabolic perturbations, revealing disruptions in central carbon metabolic fluxes and host tryptophan metabolism in at‐risk phenotype. Functional assays in primary cells and cortical forebrain organoids (FBOs) further validate this. Metabolic perturbations lead to persistent monocyte activation, thereby impairing their functions ex vivo. Furthermore, the chronic inflammatory plasma microenvironment contributes to synaptic dysregulation in FBOs. The endogenous plasma inflammatory microenvironment is responsible for chronic inflammation in treated immunometabolically complicated at‐risk PWH who have a higher risk of cardiovascular and neuropsychiatric disorders.
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Research context

OpenAlex topics: HIV Research and Treatment · HIV-related health complications and treatments · Immune cells in cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine Karolinska Institutet Huddinge 141 52 Sweden

Copenhagen University Hospital Rigshospitalet Copenhagen 2100 Denmark

Neuroscience and Mental Health Innovation Institute and School of Biosciences, Hadyn Ellis Building Cardiff University Cardiff CF24 4HQ UK

Division of Clinical Microbiology, Department of Laboratory Medicine Karolinska Institutet Huddinge 141 52 Sweden

Division of Chemistry I, Department of Medical Biochemistry and Biophysics Karolinska Institutet Solna 171 65 Sweden

Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet Oslo 0372 Norway

Norwegian PSC Research Center Oslo University Hospital Rikshospitalet Oslo 0372 Norway

Institute of Clinical Medicine University of Oslo Oslo 0313 Norway

Department of Infectious Diseases Copenhagen University Hospital – Amager and Hvidovre Hvidovre 2650 Denmark

Institute of Clinical Medicine Oslo 0372 Norway

Olink AB Uppsala 753 30 Sweden

National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics Stockholm University Solna 171 65 Sweden

Departments of Medicine and Microbiology, APC Microbiome Ireland University College Cork Cork T12 K8AF Ireland

Lung Microenvironmental Niche in Cancerogenesis, Institute for Lung Health (ILH) Justus Liebig University 35392 Giessen Germany

Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, member of the German Center for Lung Research (DZL) Member of the Cardio‐Pulmonary Institute (CPI) 61231 Bad Nauheim Germany

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet Karolinska University Hospital Huddinge 141 52 Sweden

Childhood Cancer Research Unit Department of Women's and Children's Health Karolinska Institutet Solna 171 77 Sweden

Genomics of Ageing and Rejuvenation Lab Institute of Inflammation and Ageing University of Birmingham Birmingham B15 2WB UK

Department of Molecular Immunology Helmholtz Centre for Infection Research 38124 Braunschweig Germany

Science for Life Laboratory KTH – Royal Institute of Technology Solna 171 65 Sweden

Centre for Host‐Microbiome Interactions Faculty of Dentistry Oral & Craniofacial Sciences King's College London London GW37+C7 UK

Funding

Vetenskapsrådet

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