Fig. 2.

Possible roles of viral persistence in ME/CFS, with an emphasis on the haematological, immune, and neurological system. Virus particles and/or virulent molecules are secreted from viral reservoirs (immune cells like B-cells and monocytes, endothelial cells, and neurons). Infection of neurological tissue might lead to autonomic dysfunction and subsequently the cardiovascular abnormalities observed in ME/CFS. Infection of immune cells can result in cellular senescence, reduced cell function (e.g. cytotoxicity of NK cells), and inflammatory signalling which might prompt chronic inflammation; furthermore, infected immune cells can release virus particles and/or virulent molecules into circulation. The endothelium might also act as a reservoir, where subsequent endothelial dysfunction will ensue. Secretion of virus particles and molecules into circulation can interfere with platelets and clotting machinery to influence coagulation. Hyperactivated platelets, hypercoagulability, anomalous clotting, inflammation, and O&NS stress induced by viral activity will induce further endothelial damage, possibly to the extent whereby substance exchange between blood and tissues is impaired. Created using Biorender.com.