What Causes ME/CFS: The Role of the Dysfunctional Immune System and Viral Infections

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains an enigmatic highly disabling and complex long-term condition with a wide range of aetiologies and symptoms. A viral onset is commonly mentioned by patients and several bodily systems are ultimately disturbed. The parallel with long-covid is clear. However, immune dysregulation with impaired NK cell dysfunction and tendency to novel autoimmunity have been frequently reported. These may contribute to reactivation of previous acquired viruses/retrovirusesaccompanied by impaired endocrine regulation and mitochondrial energy generation. The unpredictable nature of seemingly unconnected and diverse symptoms that are poorly responsive to several allopathic and alternative therapies then contributes to an escalation of the illness with secondary dysfunction of multiple other systems. Treatment of established ME/CFS is therefore difficult and requires multi-specialty input addressing each of the areas affected by the illness.

Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…In the past, this underfunded and misunderstood disease has occurred in clustered outbreaks, but most cases in recent years have been sporadic [4]. This knowledge and other substantial evidence imply an infectious agent at work, but its identity remains controversial [5][6][7][8]. Currently, there is no FDA-approved drug to treat individuals with ME/CFS [9].…”

Surveying the Metabolic and Dysfunctional Profiles of T Cells and NK Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Despite this illness presentation, and other significant reports implying the involvement of an infectious event, the triggering agent remains a topic of debate in the scientific community [7][8][9][10]. Several viruses have been implicated in ME/CFS, including, but not limited to, the Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and enteroviruses A and B (EV-A and EV-B) [7,8,[10][11][12][13][14][15][16].…”

Myalgic encephalomyelitis/chronic fatigue syndrome from current evidence to new diagnostic perspectives through skeletal muscle and metabolic disturbances

“…An intriguing perspective lies in the aberrant activation of human endogenous retrovirus (HERVs), that is, dormant viral sequences incorporated in our genome representing about 8% of human genome and found to be differently expressed in ME/CFS patients; this activation can be triggered by external factors, such as infections, and patients may be less capable to re‐silence HERVs 178 . Evidence for post‐viral fatigue syndrome, whose criteria were similar criteria to those proposed for CFS, has been known since decades ago, for example, due to a possible persistent enteroviral infection in the muscle, 179 and muscle fatigue may consequently arise because of the following mitochondrial damage 180 ; indeed, the neuromuscular features of ME were suggested to be a complication of subclinical enteroviral infection 181 .…”

“…181 The immune defects and infectious agent hypothesis is still advancing, nurtured by complex interaction between the immune system and viruses/retroviruses of our genome with subtle changes in cytokines, NK cells, and T cells, combined with the induced mitochondrial dysfunction. 178 A hypothesis lies in autonomic and vascular dysregulation: sympathetic overactivity in the presence of dysfunctional ß2-adrenergic receptors and endothelial dysfunction induces the release of hyperalgesic vasodilators as a compensatory response. 32 This bioenergetic and vascular hypothesis postulates that metabolic disturbance leads to calcium overload inducing poor energetic situation and endothelial dysfunction in skeletal muscle.…”

“…Evidence for post‐viral fatigue syndrome, whose criteria were similar criteria to those proposed for CFS, has been known since decades ago, for example, due to a possible persistent enteroviral infection in the muscle, 179 and muscle fatigue may consequently arise because of the following mitochondrial damage 180 ; indeed, the neuromuscular features of ME were suggested to be a complication of subclinical enteroviral infection 181 . The immune defects and infectious agent hypothesis is still advancing, nurtured by complex interaction between the immune system and viruses/retroviruses of our genome with subtle changes in cytokines, NK cells, and T cells, combined with the induced mitochondrial dysfunction 178 …”