Related Experiment Video
Updated: Aug 12, 2025
Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies
Published on: January 7, 2019
Transient Viral Rebound in Children with Perinatally Acquired HIV-1 Induces a Unique Soluble Immunometabolic
Laura Tarancon-Diez1, Joaquim Peraire2,3,4,5, Santiago Jiménez de Ory5,6
1Molecular Immunology Laboratory, Hospital General Universitario Gregorio Marañón, Health Research Institute Gregorio Marañón (IiSGM), Madrid, Spain.
Insights
Transient viral rebound (tVR) in children with perinatally acquired HIV-1 (PHIV) leads to changes in soluble proteins, lipids, and metabolites. These biomarkers correlate with immune parameters like the CD4/CD8 ratio, indicating potential for monitoring immune progression.
Area of Science:
- Biochemistry
- Immunology
- Virology
Background:
- Perinatally acquired HIV-1 (PHIV) presents unique challenges in managing viral load and immune status in children.
- Transient viral rebound (tVR), defined as a temporary increase in HIV-1 RNA levels, can occur despite antiretroviral therapy.
- Understanding the molecular consequences of tVR is crucial for assessing its impact on immune health.
Purpose of the Study:
- To investigate the multi-omic changes (metabolites, lipids, proteins) associated with transient viral rebound (tVR) in children with perinatally acquired HIV-1 (PHIV).
- To identify potential biomarkers reflecting immune status changes following tVR.
Main Methods:
- Plasma samples from children with PHIV undergoing tVR were collected immediately before (pre-tVR) and after (post-tVR) the event.
- Multi-omic analyses were performed using liquid chromatography-Orbitrap, gas chromatography-quadrupole time-of-flight mass spectrometry (GC-qTOF-MS), and liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qTOF-MS).
- Post-tVR profiles were compared to a reference group of children with PHIV and persistent viral control.
Main Results:
- While no significant changes in metabolites, lipids, or proteins were observed comparing pre- and post-tVR in the same individuals, significant differences were found when comparing post-tVR to a control group.
- Ten proteins, eight metabolites, and two lipids were significantly altered post-tVR, including upregulation of serotransferrin and succinic acid, and downregulation of alpha-2-macroglobulin and oleic acid.
- The CD4/CD8 ratio showed a trend towards decrease post-tVR and correlated with specific proteins (apolipoprotein A-II) and metabolites (methionine, diacylglyceride 34:1).
Conclusions:
- Transient viral rebound (tVR) in children with PHIV is associated with distinct changes in soluble proteins, lipids, and metabolites.
- These molecular changes correlate with key immunological parameters, particularly the CD4/CD8 ratio, which declines after tVR.
- The identified soluble biomarkers hold potential for monitoring immune progression in children living with HIV-1.
Background:
To determine by multi-omic analysis changes in metabolites, lipids, and proteins as a consequence of transient viral rebound (tVR) in children with perinatally acquired HIV-1 (PHIV).
Methods:
Plasma samples from children with PHIV and with tVR (first episode of transient RNA-HIV viral load >20 copies/ml followed by suppression) on the time-point immediately before (pre-tVR) and after (post-tVR) the tVR were assessed. Multi-omic analyses were performed using nLC-Orbitrap, GC-qTOF-MS, and LC-qTOF-MS.
Results:
Comparing pre- and post-tVR time-points, HIV-1 children with tVR (n = 5) showed a trend to a decrease in ratio CD4/CD8 (p = 0.08) but no significant differences were observed in plasma metabolites, lipids, or proteins. Post-tVR condition was compared with a reference group of children with PHIV with persistent viral control (n = 9), paired by sex, age, and time under antiretroviral treatment. A total of 10 proteins, 8 metabolites, and 2 lipids showed significant differences (p < 0.05): serotransferrin, clusterin, kininogen-1, succinic acid, threonine, 2-hydroxyisovaleric acid, methionine, 2-hydroxyglutaric, triacylglyceride 50:0 (TG50:0), and diacylglyceride 34:1 (DG34:1) were upregulated while alpha-2-macroglobulin, apolipoprotein A-II, carboxylic ester hydrolase, apolipoprotein D, coagulation factor IX, peptidase inhibitor 16, SAA2-SAA4 readthrough, oleic acid, palmitoleic acid, and D-sucrose downregulated on post-tVR time-point compared to the reference group. Ratio CD4/CD8 correlated with apolipoprotein A-II, DG34:1, and methionine (p = 0.004; ρ = 0.71, p = 0.016; ρ = -0.63; and p = 0.032; ρ = -0.57, respectively). Nadir CD4+ correlated inversely with kininogen-1 (p = 0.022; ρ = -0.60) and positively with D-sucrose (p = 0.001; ρ = 0.77).
Conclusions:
tVR followed by suppression implies changes in soluble proteins, lipids, and metabolites that correlate with immunological parameters, mainly ratio CD4/CD8, that decreased after tVR. These distinct soluble biomarkers could be considered potential biomarkers of immune progression.
Related Concept Videos
01:26Size and Structure of Viral Genomes
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
01:10Retrovirus Life Cycles