Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back!

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) is a chronic multisystem illness of unconfirmed etiology. There are currently no biomarkers and/or signatures available to assist in the diagnosis of the syndrome and while numerous mechanisms have been hypothesized to explain the pathology of ME/CFS, the triggers and/or drivers remain unknown. Initial studies suggested a potential role of the human herpesviruses especially Epstein-Barr virus (EBV) in the disease process but inconsistent and conflicting data led to the erroneous suggestion that these viruses had no role in the syndrome. New studies using more advanced approaches have now demonstrated that specific proteins encoded by EBV could contribute to the immune and neurological abnormalities exhibited by a subgroup of patients with ME/CFS. Elucidating the role of these herpesvirus proteins in ME/CFS may lead to the identification of specific biomarkers and the development of novel therapeutics.

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Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome

Frontiers in Immunology ◽

10.3389/fimmu.2021.656797 ◽

2021 ◽

Vol 12 ◽

Author(s):

Manuel Ruiz-Pablos ◽

Bruno Paiva ◽

Rosario Montero-Mateo ◽

Nicolas Garcia ◽

Aintzane Zabaleta

Keyword(s):

T Cell ◽

Chronic Fatigue Syndrome ◽

Epstein Barr Virus ◽

Chronic Fatigue ◽

Myalgic Encephalomyelitis ◽

Th2 Response ◽

Barr Virus ◽

Fatigue Syndrome ◽

Cell Immunity ◽

Epstein Barr

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) affects approximately 1% of the general population. It is a chronic, disabling, multi-system disease for which there is no effective treatment. This is probably related to the limited knowledge about its origin. Here, we summarized the current knowledge about the pathogenesis of ME/CFS and revisit the immunopathobiology of Epstein-Barr virus (EBV) infection. Given the similarities between EBV-associated autoimmune diseases and cancer in terms of poor T cell surveillance of cells with EBV latency, expanded EBV-infected cells in peripheral blood and increased antibodies against EBV, we hypothesize that there could be a common etiology generated by cells with EBV latency that escape immune surveillance. Albeit inconclusive, multiple studies in patients with ME/CFS have suggested an altered cellular immunity and augmented Th2 response that could result from mechanisms of evasion to some pathogens such as EBV, which has been identified as a risk factor in a subset of ME/CFS patients. Namely, cells with latency may evade the immune system in individuals with genetic predisposition to develop ME/CFS and in consequence, there could be poor CD4 T cell immunity to mitogens and other specific antigens, as it has been described in some individuals. Ultimately, we hypothesize that within ME/CFS there is a subgroup of patients with DRB1 and DQB1 alleles that could confer greater susceptibility to EBV, where immune evasion mechanisms generated by cells with latency induce immunodeficiency. Accordingly, we propose new endeavors to investigate if anti-EBV therapies could be effective in selected ME/CFS patients.

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Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Clinical Therapeutics ◽

10.1016/j.clinthera.2019.04.009 ◽

2019 ◽

Vol 41 (5) ◽

pp. 848-863 ◽

Cited By ~ 5

Author(s):

Marshall V. Williams PhD ◽

Brandon Cox ◽

William P. Lafuse PhD ◽

Maria Eugenia Ariza

Keyword(s):

Chronic Fatigue Syndrome ◽

Epstein Barr Virus ◽

Chronic Fatigue ◽

Myalgic Encephalomyelitis ◽

Barr Virus ◽

Fatigue Syndrome ◽

Epstein Barr

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Epstein-Barr Virus Induced Gene-2 Upregulation Identifies a Particular Subtype of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Frontiers in Pediatrics ◽

10.3389/fped.2019.00059 ◽

2019 ◽

Vol 7 ◽

Cited By ~ 5

Author(s):

Jonathan R. Kerr

Keyword(s):

Chronic Fatigue Syndrome ◽

Epstein Barr Virus ◽

Chronic Fatigue ◽

Myalgic Encephalomyelitis ◽

Barr Virus ◽

Fatigue Syndrome ◽

Epstein Barr

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Post Viral Chronic Fatigue Syndrome: Persistence of Epstein-Barr Virus DNA in Muscle

Epstein-Barr Virus and Human Disease • 1988 ◽

10.1007/978-1-4612-4508-7_61 ◽

1989 ◽

pp. 439-444

Author(s):

Leonard C. Archard ◽

John L. Peters ◽

Peter O. Behan ◽

David Doyle ◽

Michael Mackett ◽

...

Keyword(s):

Chronic Fatigue Syndrome ◽

Epstein Barr Virus ◽

Chronic Fatigue ◽

Barr Virus ◽

Fatigue Syndrome ◽

Epstein Barr

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Overview

Journal of Clinical Medicine ◽

10.3390/jcm10204786 ◽

2021 ◽

Vol 10 (20) ◽

pp. 4786

Author(s):

Undine-Sophie Deumer ◽

Angelica Varesi ◽

Valentina Floris ◽

Gabriele Savioli ◽

Elisa Mantovani ◽

...

Keyword(s):

Cognitive Impairment ◽

Chronic Fatigue Syndrome ◽

Systemic Disease ◽

Disease Onset ◽

Chronic Fatigue ◽

Myalgic Encephalomyelitis ◽

Diagnostic Tools ◽

Fatigue Syndrome ◽

Non Coding Rna

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic systemic disease that manifests via various symptoms such as chronic fatigue, post-exertional malaise, and cognitive impairment described as “brain fog”. These symptoms often prevent patients from keeping up their pre-disease onset lifestyle, as extended periods of physical or mental activity become almost impossible. However, the disease presents heterogeneously with varying severity across patients. Therefore, consensus criteria have been designed to provide a diagnosis based on symptoms. To date, no biomarker-based tests or diagnoses are available, since the molecular changes observed also largely differ from patient to patient. In this review, we discuss the infectious, genetic, and hormonal components that may be involved in CFS pathogenesis, we scrutinize the role of gut microbiota in disease progression, we highlight the potential of non-coding RNA (ncRNA) for the development of diagnostic tools and briefly mention the possibility of SARS-CoV-2 infection causing CFS.

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