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Plasma EBV microRNAs in paediatric renal transplant recipients
Jaythoon Hassan1, Jonathan Dean2, Cillian F De Gascun2
1National Virus Reference Laboratory, University College Dublin, Belfield, Dublin 4, Ireland. jaythoon.hassan@ucd.ie.
Background:
Epstein-Barr virus (EBV) was the first human virus identified to express microRNA (miRNA). To date, 44 mature miRNAs are encoded for within the EBV genome. EBV miRNAs have not been profiled in paediatric renal transplant recipients. In this study, we investigated circulating EBV miRNA profiles as novel biomarkers in paediatric renal transplant patients.
Methods:
Forty-two microRNAs encoded within 2 EBV open reading frames (BART and BHRF) were examined in renal transplant recipients who resolved EBV infection (REI) or maintained chronic high viral loads (CHL), and in non-transplant patients with acute infectious mononucleosis (IM).
Results:
Plasma EBV-miR-BART2-5p was present in higher numbers of IM (7/8) and CHL (7/10) compared to REI (7/12) patients. A trend was observed between the numbers of plasma EBV miRNAs expressed and EBV viral load (p < 0.07). Several EBV-miRs including BART7-3p, 15, 9-3p, 11-3p, 1-3p and 3-3p were detected in IM and CHL patients only. The lytic EBV-miRs, BHRF1-2-3p and 1-1, indicating active viral replication, were detected in IM patients only. One CHL patient developed post-transplant lymphoproliferative disease (PTLD) after several years and analysis of 10 samples over a 30-month period showed an average 24-fold higher change in plasma EBV-miR-BART2-5p compared to the CHL group and 110-fold higher change compared to the REI group.
Conclusions:
Our results suggest that EBV-miR-BART2-5p, which targets the stress-induced immune ligand MICB to escape recognition and elimination by NK cells, may have a role in sustaining high EBV viral loads in CHL paediatric kidney transplant recipients.
Insights
Epstein-Barr virus (EBV) microRNAs (miRNAs) were profiled in pediatric kidney transplant patients. EBV-miR-BART2-5p may sustain high viral loads in chronic high EBV patients, potentially aiding in post-transplant lymphoproliferative disease development.
Area of Science:
- Virology
- Immunology
- Transplantation
Background:
- Epstein-Barr virus (EBV) was the first human virus found to express microRNAs (miRNAs).
- 44 mature miRNAs are encoded in the EBV genome.
- EBV miRNA profiles in pediatric renal transplant recipients have not been previously studied.
Purpose of the Study:
- To investigate circulating EBV miRNA profiles as potential biomarkers in pediatric renal transplant patients.
- To explore the role of EBV miRNAs in different EBV infection states post-transplantation.
Main Methods:
- Examined 42 EBV miRNAs from BART and BHRF open reading frames.
- Analyzed samples from renal transplant recipients with resolved EBV infection (REI) or chronic high viral loads (CHL).
- Included non-transplant patients with acute infectious mononucleosis (IM) as controls.
Main Results:
- Plasma EBV-miR-BART2-5p was elevated in IM and CHL patients compared to REI patients.
- A trend suggested a correlation between EBV miRNA levels and EBV viral load.
- Specific EBV-miRs were detected only in IM and CHL patients, while lytic EBV-miRs were found only in IM patients.
- One CHL patient who developed post-transplant lymphoproliferative disease (PTLD) showed significantly higher EBV-miR-BART2-5p levels.
Conclusions:
- EBV-miR-BART2-5p may contribute to maintaining high EBV viral loads in CHL pediatric kidney transplant recipients.
- This miRNA targets MICB to evade NK cell recognition, potentially playing a role in PTLD development.
- Circulating EBV miRNAs show promise as biomarkers in pediatric renal transplant recipients.
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