Suhadolnik, R J, Reichenbach, N L, Hitzges, P et al. · Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 1994 · DOI
This study found that people with ME/CFS have overactive immune signaling molecules called the 2-5A pathway in their blood cells, which normally fight viral infections. When patients received an experimental treatment, this overactive pathway calmed down and they improved clinically, and the researchers also found signs of a herpesvirus in almost all CFS patients tested.
This study provides mechanistic evidence linking persistent viral infection (HHV-6) and abnormal antiviral immune activation to ME/CFS, suggesting a potential biological basis for the disease. The finding that immune pathway normalization correlated with clinical improvement offers a testable hypothesis for future therapeutic development.
This study does not prove that HHV-6 causes ME/CFS, only that it was detected in these patients and that immune activation occurred. The small sample size, lack of a placebo control group, and temporal association between treatment and improvement do not establish causation. The findings cannot be generalized to all ME/CFS patients.
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
Suhadolnik, R J, Reichenbach, N L, Hitzges, P, Sobol, R W, Peterson, D L, Henry, B, et al. (1994). Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome.. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. https://doi.org/10.1093/clinids/18.supplement_1.s96
BibTeX
@article{mecfsatlas-suhadolnik-1994-upregulation-synthetase,
author = {Suhadolnik, R J and Reichenbach, N L and Hitzges, P and Sobol, R W and Peterson, D L and Henry, B and Ablashi, D V and Müller, W E and Schröder, H C and Carter, W A},
title = {Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
year = {1994},
doi = {10.1093/clinids/18.supplement_1.s96},
note = {PubMed: 8148461},
url = {https://www.mecfsatlas.com/evidence/suhadolnik-1994-upregulation-synthetase},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/suhadolnik-1994-upregulation-synthetase
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