Researchers
Karen Giménez-Orenga, Eva Martín-Martinez, Lubov Nathanson, Elisa Oltra
Institutions
Catholic University of Valencia and Manises Hospital, Valencia, Spain; Nova Southeastern University, Fort Lauderdale, Florida, USA
Publication
eLife, 2025; 14:RP104441
Funding
ME Research UK
Key findings
- Human endogenous retrovirus (HERV) expression was assessed in immune cell samples from four groups of women: those with ME/CFS, fibromyalgia or both conditions, and healthy controls.
- HERVs are a family of viruses contained within the human genome and which may have a role in the development of some diseases.
- The HERV expression profiles generated could accurately distinguish between these four subject groups.
- These “HERV fingerprints” may therefore be valuable in the diagnosis of ME/CFS and fibromyalgia, but the findings need to be replicated in larger groups.
About the study
Human endogenous retroviruses (HERVs) are a family of viruses contained within the human genome – that is, their DNA has become part of our DNA and is passed on from generation to generation.
Most HERVs are thought to be inactive, but there is evidence that some may have a role in the development of diseases such as multiple sclerosis and type 1 diabetes. Activated HERVs may lead to the stimulation of an immune response, contributing to the symptoms of disease.
HERVs have also been proposed as potential triggers of ME/CFS, and two previous studies have reported overexpression of some HERV families in the immune cells of people with the disease.
Prof. Elisa Oltra and her team at the Catholic University of Valencia have been investigating the role of HERVs in ME/CFS in an ME Research UK-funded study, and in this paper they compare HERV expression profiles between four groups of women with ME/CFS and/or fibromylalgia.
What did they do?
The researchers compared four groups of female subjects: 8 patients with ME/CFS (diagnosed using the Canadian and International Consensus criteria), 10 with fibromyalgia (diagnosed using the American College of Rheumatology criteria), 16 with both ME/CFS and fibromyalgia, and 9 healthy controls.
Blood samples were taken from all participants, and peripheral blood mononuclear cells were isolated, many of which play important roles in the immune system. RNA was then extracted from these cells. RNA is a molecule which uses the genetic information in DNA to build proteins, and some viruses have RNA as their main genetic material.
High-density microarray technology was then used to assess HERV expression profiles in these samples, characterising which specific HERVs were over- or under-expressed in each sample.
What did they find?
Remarkably, these profiles could accurately distinguish between the four subject groups; i.e. the patterns of over- or under-expression of different HERVs were characteristic for each disease, and different from that in healthy control subjects.
This raises the intriguing possibility that these “HERV fingerprints” may be valuable in the diagnosis of ME/CFS and fibromyalgia. However, these findings would need to be replicated in larger groups.
The results also indicate increased dysregulation of HERV in patients with ME/CFS, compared with those with fibromylagia, both conditions, or healthy controls. Furthermore, the ME/CFS group could be divided into two subgroups with different levels of MERV expression profiles, and associated with different levels of fatigue. The authors suggest these differences may therefore help in the assessment of ME/CFS severity.
Conclusions
The researchers have identified “HERV fingerprints” which can distinguish between women with ME/CFS, those with fibromyalgia, those with both conditions, and healthy controls. These may therefore have value in the diagnosis of these conditions, although the findings need validation in larger groups.
The results also give clues about the underlying pathology of ME/CFS, including the influence of epigenetic factors on HERV function.
