The effect of activated HERVs and the associated immune response in severe ME/CFS

Principal investigator

Prof. Elisa Oltra


Catholic University of Valencia, Valencia, Spain

Start date

December 2020

Background and aim

Epigenetics has become a very promising field in the search for explanations about how ME/CFS develops. It refers to the many ways in which our body can turn our genes on or off in a cell, which in turn determines what function that cell ultimately performs.

ME Research UK has previously provided funding for research studies investigating epigenetics, including the work of Prof. Jo Nijs and Prof. Lode Godderis in Belgium, who have found increased levels of brain-derived neurotropic factor (BDNF) in people with ME/CFS, and are now looking at how epigenetic changes in BDNF and HDACs may be involved in post-exertional malaise.

Cort Johnson has written an excellent article for us, introducing the field and discussing the relevance of epigenetics to ME/CFS, and you can read that here.

Another tantalising prospect is that epigenetics may be involved in the link between the presence of human endogenous retroviruses (HERVs) and the development of ME/CFS. This is the area that Prof. Elisa Oltra and her team at the Catholic University of Valencia in Spain are investigating in their study awarded funding by ME Research UK.

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. Despite making up 8% of our genome, most are generally thought to be dormant.

However, there is evidence that some HERVs may have a role in the development of diseases such as multiple sclerosis, type 1 diabetes and schizophrenia (and maybe COVID-19). And HERVs have also been proposed as potential triggers of ME/CFS.

Prof. Oltra’s hypothesis is that epigenetic changes cause activation of HERVs, which then leads to an innate immune response and the resulting flu-like symptoms and autoimmune problems that are characteristic of ME/CFS.

In her study funded by ME Research UK, she plans to identify HERVs that are overexpressed in a group of 12 women with severe ME/CFS compared with a matched group of women with fibromyalgia.

The team will also look at the effects of activation of these ME-associated HERVs on nerve and muscle cells in laboratory conditions, to understand their potential impact on the symptoms of the illness.

The results will then be validated in an extended group of 50 women with ME/CFS, 25 with fibromyalgia, and 25 healthy control subjects.

Prof. Oltra’s hope is that these HERV ‘fingerprints’ could be used in the diagnosis of ME/CFS, or for patient subtyping. But her findings will also help establish whether activation of HERVs might be at the root of the disease. Furthermore, the cell model she is developing could be a valuable tool in the future for assessing potential treatments for ME/CFS.

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