Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses.
Apostolou, Eirini, Rosén, Anders · Journal of internal medicine · 2024 · DOI
Quick Summary
This review examines how viruses, particularly Epstein-Barr virus, may cause lasting changes to how our cells work in ME/CFS patients. The authors found that in about 70% of ME/CFS cases, the illness begins after a viral infection, and viruses can hide in the body while triggering long-term problems with energy, thinking, and immune function. Understanding these viral-triggered changes could help explain why different patients experience ME/CFS differently and may lead to better treatments.
Why It Matters
This work provides a mechanistic framework linking viral infections to the multi-system dysfunction observed in ME/CFS, which could guide research toward epigenetic biomarkers and targeted interventions. Understanding how viruses manipulate cellular regulation may reveal why ME/CFS symptoms persist long after acute infection and why some patients deteriorate with exertion. This knowledge is particularly relevant given the overlaps between ME/CFS and long COVID.
Observed Findings
- Approximately 70% of ME/CFS cases follow a major stressor involving viral infection
- Epigenetic alterations in ME/CFS affect immune responses, cellular metabolism, cell death/proliferation, and neuronal/endothelial function
- Latent herpesviruses, particularly Epstein-Barr virus, employ epigenetic regulation strategies for persistence and immune evasion
- Clinical and symptom overlap exists between ME/CFS and long COVID
- Physiological variations among ME/CFS patients correlate with environmental triggers and altered viral activity patterns
Inferred Conclusions
- Latent herpesvirus-driven epigenetic reprogramming may be a key mechanism underlying persistent ME/CFS pathology
- Epigenetic signatures in ME/CFS reflect the dynamic interaction between viral persistence strategies and host immune responses
- Epigenetic biomarkers could help identify relevant biological pathways affected in ME/CFS and potentially stratify patient heterogeneity
- Future epigenetic research may elucidate why symptoms persist despite immune activation and could inform therapeutic targeting
Remaining Questions
- Which specific epigenetic modifications are causally linked to ME/CFS symptoms versus secondary consequences of chronic illness?
- Do epigenetic signatures differ predictably based on which virus triggered the illness (EBV vs. other herpesviruses)?
- Can epigenetic biomarkers predict patient prognosis or guide treatment selection in ME/CFS?
- What environmental factors or genetic backgrounds determine whether viral infection leads to ME/CFS versus full recovery in some individuals?
What This Study Does Not Prove
This narrative review does not establish definitive causal relationships between specific viruses and ME/CFS—it synthesizes existing evidence without new experimental data. It does not prove that viral reactivation occurs in all ME/CFS patients or that targeting viral epigenetic mechanisms will reverse symptoms. The review cannot determine whether observed epigenetic changes are primary causes of ME/CFS or secondary consequences of systemic illness.
Topics
Tags
Metadata
- DOI
- 10.1111/joim.13792
- PMID
- 38693641
- Review status
- Machine draft
- Evidence level
- Established evidence from major reviews, guidelines, or evidence maps
- Last updated
- 7 April 2026