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Reactivation of herpesviruses in Myalgic Encephalomyelitis

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome affects an estimated 24 million people worldwide, of whom around a quarter are severely affected and are house- or bed-bound, and it strikes people in their prime of life, causing enormous personal and societal economic costs. Few people recover completely from ME/CFS, although symptoms can fluctuate. There is no diagnostic test for ME/CFS, and the lack of understanding of disease mechanisms is preventing the development of rational treatments.

There is an overlap in clinical presentation with some people experiencing Long COVID, including post-viral fatigue and brain fog, potentially caused by similar disease mechanisms. It is characterised by persistent or recurrent incapacitating fatigue and the worsening of symptoms following even minor physical or mental exertion, alongside symptoms affecting the immune, endocrine and neural systems.

Human Herpesviruses (HHVs) have been speculatively implicated in ME/CFS pathogenesis, but there is no correlation between infection per se and ME/CFS development. Most people are infected with HHVs early in life and do not experience any symptoms due to an effective immunological system.

We hypothesise that the characteristic persistent remitting and relapsing nature of the ME/CFS syndrome in many individuals is the result of repeated HHV-6B reactivation, due to abnormal immune responses in susceptible people following an initial triggering event such as infection with another virus. In a small pilot study, we found that the concentration of DNA from HHV-6B was higher in saliva from people with ME/CFS, and that the concentration correlated with the severity of symptoms.

We were unable to determine whether HHV-6B reactivation directly caused the symptoms, or whether it was a result of another ME/CFS disease process.

In our current project, we are performing a larger-scale prospective virologic study, with people with mild/moderate or severe ME/CFS alongside healthy people. We are asking our study participants to record their symptom severity frequently, so that we can determine whether changes in HHV-6B concentration in saliva occur before or after changes in ME/CFS symptoms.

In this way, we aim to determine whether HHV-6B causes the symptom changes or if these occur after the disease gets worse. We are also investigating immune cell function in people with ME/CFS and/or Long COVID: specifically, we are looking at cytotoxic T cells, including their responses to stimulation and at the impact of HHV-6B on their interaction with other immune cells.

We will gain a better understanding of the role of herpesviruses, particularly HHV-6B, in the onset and progression of ME/CFS and Long COVID, which will lead to the development of specific drug treatments, including anti-viral therapy and drugs to boost the immune system appropriately. It will also help with the development of diagnostic and prognostic markers for ME/CFS.


  • Lee J-S., Lacerda EM., Nacul L., Kingdon CC., Norris J., O'Boyle S., Roberts CH., Palla L., Riley EM. and Cliff JM. (2021) 'Salivary DNA Loads for Human Herpesviruses 6 and 7 Are Correlated With Disease Phenotype in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome'. Frontiers in Medicine, 8. pp. 656692.
  • Cliff JM., King EC., Lee J-S., Sepúlveda N., Wolf A-S., Kingdon C., Bowman E., Dockrell HM., Nacul L., Lacerda E. and Riley EM. (2019) 'Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)'. Frontiers in Immunology, 10. pp. 796.
  • O'Boyle S., Nacul L., Nacul FE., Mudie K., Kingdon CC., Cliff JM., Clark TG., Dockrell HM. and Lacerda EM (2021). “A Natural History of Disease Framework for Improving the Prevention, Management, and Research on Post-viral Fatigue Syndrome and Other Forms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”. Frontiers in Medicine 8. pp. 688159.
  • Nacul L., de Barros B., Kingdon CC., Cliff JM. Clark TG., Mudie K., Dockrell HM and Lacerda EM. (2019) ‘Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study’. Diagnostics 9. pp.41.

Meet the Principal Investigator(s) for the project

Jacqueline Cliff
Jacqueline Cliff - Jackie read Physiological Sciences at the University of Oxford, followed by an MSc in the Immunology of Infectious Diseases at the London School of Hygiene & Tropical Medicine. She then moved to the National Institute for Medical Research for her PhD, where she investigated the role of cytokines in B cell activation and differentiation with Dr Gerry Klaus. Jackie worked with Prof Hazel Dockrell at LSHTM (1999-2022), mainly studying immune responses in tuberculosis and how these could be utilised to assess responses to antibiotic treatment. More recently, her research has also encompassed comorbidities such as diabetes in tuberculosis, and expanded to include the role of the infection and immunity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome.     Jackie joined Brunel University in March 2022, combining her research in the Biosciences Division with her teaching within the Medical School.

Related Research Group(s)

human body

Inflammation Research and Translational Medicine - Driving scientific innovation and discovery for diagnosis, treatment, and management of cardiovascular disease, inflammatory and immune disorders, microbial resistance, and cancer.

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Project last modified 16/11/2023