The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome

Abstract

Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disease with an unexplained aetiology in which viral infections are possible trigger factors. The aim of this study was to determine the involvement of human herpesvirus (HHV)-6A/B, HHV-7, and parvovirus B19 (B19V) in the etiopathogenesis of ME/CFS. Methods 200 patients with clinically diagnosed ME/CFS and 150 apparently healthy individuals were enrolled in this study. Single-round, nested, and quantitative real-time polymerase chain reactions (PCR) were used to detect the presence and load of HHV-6A/B, HHV-7, and B19V. HHV-6A and HHV-6B were distinguished by PCR and restriction analysis. Immunoenzymatic assays were applied to estimate the presence of virus-specific antibodies and the level of cytokines. Results HHV-6A/B, HHV-7, and B19V specific antibodies were detected among patients and healthy individuals in 92.1% and 76.7%, 84.6% and 93.8%, and 78% and 67.4% of cases. HHV-6B had 99% of HHV-6 positive patients. Latent HHV-6A/B, HHV-7, and B19V infection/co-infection was observed in 51.5% of the patients and 76.7% of the healthy individuals, whereas active–45% of the ME/CFS patients and 8.7% of healthy individuals. HHV-6A/B load in patients with a persistent infection/co-infection in a latent and active phase was 262 and 653.2 copies/106 cells, whereas HHV-7 load was 166.5 and 248.5 copies/106 cells, and B19V-96.8 and 250.8 copies/106 cells, respectively. ME/CFS patients with persistent infection in an active phase had a higher level of pro-inflammatory cytokines (interleukin(IL)-6, tumor necrosis factor-alpha(TNF-α) and IL-12) and anti-inflammatory (IL-10) than with a persistent infection in a latent phase. A significant difference was revealed in the levels of TNF-α, IL-12, and IL-10 among the patient groups without infection, with latent infection/co-infection, active single, double and triple co-infection. The levels of TNF-α, IL-12, and IL-10 are significantly higher in patients with severe compared with a moderate course of ME/CFS. Conclusions Significantly more persistent HHV-6A/B, HHV-7, and B19V infection/co-infection in an active phase with a higher viral load and elevated levels of pro- and anti-inflammatory cytokines among patients with ME/CFS than healthy individuals indicate the importance of these infections/co-infections in ME/CFS development. The presence of these infections/co-infections influences the ME/CFS clinical course severity.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A preliminary survey among patients in Switzerland

“…Recent research suggest that EBV may be an important risk factor for the development of ME/CFS – at least in a sub-group of patients, linked with immune dysfunctions and/or genetic predisposition, and could contribute to the observed neuro-immunological impairments seen in ME/CFS patients [ [54] , [55] , [56] , [57] ]. A review by Rasa et al (2021) showed that viral diseases such as human herpesviruses, enteroviruses and huan parvovirus B19 were associated with ME/CFS onset and likely caused the irreversible immunological impairments observed, rather than causing chronic or latent viral infections [ 58 ]. Several other agents have been associated with ME/CFS in the literature (e.g.…”

Cardiovascular and haematological pathology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A role for viruses

“…Furthermore, autoimmunity driven by defective B-cell functioning is suspected to bring about autoreactivity which in turn contributes to symptom manifestation [ 127 , 230 , 256 , 257 ]. There are many other studies demonstrating increased antibody levels directed at herpesviruses (not only EBV) in ME/CFS [ 30 , [258] , [259] , [260] , [261] , [262] , [263] ]. More recent studies have identified herpesvirus nucleic acids and antigens, in significant concentrations, in ME/CFS tissue [ 32 , 60 , 263 , 264 ].…”

“…There are many other studies demonstrating increased antibody levels directed at herpesviruses (not only EBV) in ME/CFS [ 30 , [258] , [259] , [260] , [261] , [262] , [263] ]. More recent studies have identified herpesvirus nucleic acids and antigens, in significant concentrations, in ME/CFS tissue [ 32 , 60 , 263 , 264 ]. Rasa- Dzelzkaleja et al (2023) showed that 45% of ME/CFS individuals within their study were experiencing reactivation of herpesviruses (HHV-6 and HHV-7), and that these individuals expressed higher proinflammatory markers (IL-6, TNF-α) than those ME/CFS individuals with latent infection.…”

Herpesvirus Infection of Endothelial Cells as a Systemic Pathological Axis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition characterized by unresolved fatigue, cognitive dysfunction, malaise, orthostatic issues, and post-exertional symptom exacerbation (PESE), among other symptoms [ 1 ]. The etiological cause is officially unknown, but viral infection is believed to be a precipitating factor, and its pathology is very much associated with viral activity [ 2 , 3 , 4 , 5 ].…”

“…However, here, we aim to focus on herpesviruses and the endothelium or associated tissues. There are a number of different herpesviruses, but the focus here is on the ones significantly implicated in ME/CFS, namely HHV-4 (EBV) and HHV-6 [ 2 , 3 , 4 , 5 , 57 , 58 ]. For an overview of the ideas presented in this paper, as well as a mind map for clarification, see Figure 1 .…”