From: Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
Viruses | Contribution in ME/CFS |
---|---|
Human herpesviruses | Persist after primary infection in latent phase and can reactivate causing lytic virus replication Infected cells are recognized by immune system resulting in chronic inflammation that causes ME/CFS symptoms Disturb first class major histocompatibility complex (MHC) molecules presenting virus antigen Alter NK, T and B cell function Modify expression of cellular transcripts Trigger immune dysregulation Alter cytokine production resulting in appearance of ME/CFS typical symptoms Contribute in affecting signalling pathways to proper immune response Activate humoral immune response by herpesviruses-encoded dUTPases Infect neurons and immune cells to impair CNS capillaries and micro-arteries, leading to brain damage Produce a pro-inflammatory environment and autoimmune activity Damage tissue, leads to inflammation and may activate auto-reactive T and B cells, thereby contributing to autoimmunity Local virus-associated inflammation of nervous structures results in altered CNS and PNS signalling Alter ATP homeostasis, increase ROS, change mitochondrial metabolism and modulate mitochondrial DNA content |
Enteroviruses | Infect various tissue (blood, gastric, muscle, brain) and stool Persistence of viral RNA could contribute to muscle dysfunction Induce tissue damage Dysregulate host microRNAs Induce greater oxidative stress, inflammation, and pro-inflammatory M1 macrophage activity Induced inflammation can result in bystander activation of auto-reactive cells Coxsackie B4 virus infects beta cells leading to NK cell induced non-destructive inflammation Severe acute enterovirus 71 infection diminishes number of NK and T cells and induces ROS accumulation |
Parvovirus B19 | After primary infection and acute phase can establish persistent infection and lead to the manifestation of ME/CFS Interacts directly with cells leading to a more aggressive fibroblast function and degradation of cartilage matrix Active infection is linked to an increased frequency of joint pain VP1 protein affects arachidonic acid metabolism promoting inflammatory reactions NS1 protein stimulates pro-inflammatory cytokines production causing local inflammation Activates NK cells Causes neuroinflammation Contributes to greater expression of the human CFS-associated genes NHLH1 and GABPA May induce autoimmunity |
Retroviruses | No contribution |
Ross-River virus | Infect macrophages using antibody-dependent enhancement mechanism Suppresses transcription and translation of antiviral genes Generate neurocognitive manifestations affected by functional polymorphisms in cytokine genes Cause joint pain, persistent tiredness, lethargy, myalgia, lymphadenopathy, headache and depression |