Mena Palomo et al. (2026)
- Authors: Irene Mena Palomo, Brandon Cox, Marshall V. Williams, Maria Eugenia Ariza
- Institutes: Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, Ohio, USA, Institute for Behavioral Medicine Research (IBMR), The Ohio State University Wexner Medical Center, Columbus, Ohio, USA, Department of Cancer Biology and Genetics (CBG), The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- Publisher: Journal of Medical Virology
- Link: DOI
Summary
This research identifies a clear biological signature linking persistent viral activity to the severe fatigue experienced by ME/CFS patients. By demonstrating that most patients have evidence of multiple dormant viruses undergoing abortive reactivation, the study offers a potential new biomarker to test for the disease and group patients by clinical severity. These findings support the theory that ME/CFS is driven by a recurring immune response to viral proteins, which could lead to more targeted diagnostic tools and therapeutic interventions.
What was researched?
This study investigated the presence of IgG antibodies against viral dUTPase proteins from human herpesviruses and endogenous retroviruses in patients with ME/CFS. Researchers specifically examined antibodies related to Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), varicella-zoster virus (VZV), and HERV-K.
Why was it researched?
ME/CFS often follows a viral infection, yet traditional tests frequently fail to find active viral replication. This research focused on ‘abortive lytic reactivation,’ where viruses produce specific inflammatory proteins like dUTPase without completing a full replication cycle, potentially driving chronic symptoms.
How was it researched?
The researchers conducted a longitudinal analysis of 873 serum samples from 40 ME/CFS patients and 378 samples from 16 healthy controls. They used Enzyme-Linked Immunosorbent Assays (ELISA) to measure specific antibody levels and correlated these findings with the patients’ reported fatigue severity using statistical modeling.
What has been found?
A significant increase in dUTPase IgG antibodies for EBV, HHV-6, and VZV was discovered in ME/CFS patients compared to healthy controls. Notably, 72.5% of patients simultaneously expressed antibodies to multiple viruses, and these heightened antibody levels were strongly associated with moderate to severe fatigue levels.
Discussion
The results suggest that chronic, low-level reactivation of several persistent viruses is a recurrent hallmark of the disease. This multi-viral reactivation explains some of the symptom heterogeneity in ME/CFS and highlights the limitations of testing for only one virus at a single point in time.
Conclusion & Future Work
Herpesvirus dUTPase antibodies are promising biomarkers for the diagnosis and stratification of ME/CFS patients. These findings emphasize the importance of monitoring viral protein responses across different severity groups to improve clinical characterization.