Cox, Brandon S, Alharshawi, Khaled, Mena-Palomo, Irene et al. · JCI insight · 2022 · DOI
This study found that some people with ME/CFS have abnormal immune responses linked to past infections with Epstein-Barr virus (EBV) and human herpesvirus 6A (HHV-6A). The researchers discovered that proteins from these viruses may trigger the immune system to produce excess amounts of certain signaling molecules, leading to confused immune cell behavior. This suggests a possible biological mechanism for how these common viruses might contribute to ME/CFS symptoms in some patients.
This study provides a testable mechanistic pathway linking persistent EBV/HHV-6A infection to immune dysfunction in ME/CFS, potentially explaining post-infectious ME/CFS in a subset of patients. Understanding this mechanism could lead to diagnostic biomarkers and targeted therapeutic interventions. The work validates the biological plausibility of viral involvement in ME/CFS pathophysiology.
This study does not prove that EBV or HHV-6A directly causes ME/CFS or that dUTPases are the sole causative mechanism. The findings are correlational and based on in vitro and animal models; the causal relationship in humans remains unestablished. The study cannot determine whether dUTPase-driven immune abnormalities are a primary driver or a consequence of ME/CFS pathology.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Cox, Brandon S, Alharshawi, Khaled, Mena-Palomo, Irene, Lafuse, William P, & Ariza, Maria Eugenia (2022). EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities.. JCI insight. https://doi.org/10.1172/jci.insight.158193
BibTeX
@article{mecfsatlas-cox-2022-ebv-hhv,
author = {Cox, Brandon S and Alharshawi, Khaled and Mena-Palomo, Irene and Lafuse, William P and Ariza, Maria Eugenia},
title = {EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities.},
journal = {JCI insight},
year = {2022},
doi = {10.1172/jci.insight.158193},
note = {PubMed: 35482424},
url = {https://www.mecfsatlas.com/evidence/cox-2022-ebv-hhv},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/cox-2022-ebv-hhv
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