@Hip given the myriad of different infectious triggers and cases without an infectious trigger, isn't it possible that any viral particles found in tissue are incidental to autoimmunity / immune dysfunction, are not causal, and would not be problematic with a normal immune system?
That is always a logical possibility: that the infection triggers ME/CFS by causing say autoimmunity or some other immune dysfunction; but then after this triggering event, the virus plays no further role in the maintaining the disease. The disease is able to maintain itself without the further assistance from the virus — that's feasible.
And there seems to be cases of ME/CFS triggered by vaccination, which perhaps adds weight to this idea that this is a trigger-able disease that does not need any chronic viral infection to drive it, and once triggered, the disease maintains itself.
However, I think the evidence that tends to argue against this possibility is the antiviral and immunomodulatory treatments of ME/CFS, such as interferon, ribavirin or oxymatrine for enterovirus-associated ME/CFS; and Valcyte, Valtrex, cidofovir or foscarnet for herpes virus-associated ME/CFS.
With these, we tend to see a correlation with reduced viral load and reduced ME/CFS symptoms (and occasionally full remissions) when these antiviral treatments are given; and when the treatments are stopped, we often see the reverse: increased viral load and increased ME/CFS symptoms returning.
So that suggests that these viruses are playing some sort of role in ME/CFS, at the very least being a partial maintaining factor in the disease, and at the very most, the sole and only maintaining factor.
Also, going back to vaccination, it's possible (in fact probable) that someone already has one or more ME/CFS-associated viruses in their body, and thus perhaps a propensity to develop ME/CFS. Then when a trigger like a vaccination comes along, it works in conjunction with those existing viruses already in the body.
That is speculation, but if you look at the autoimmune disease of multiple sclerosis, which is linked to EBV by good evidence, people usually catch EBV when they are a teenager or in their 20s; but MS may only appear decades later in life. So if EBV is the cause of MS, we see that EBV just waits patiently for years the opportunity to instigate MS.
To play devil's advocate to my own question, maybe some have a chronic infection driving their immune activation, others have faulty b-cells, and some have both, and that there is a potential for self correction (that differs by individual) depending on what their issue is and where you address the problem.
Yes, the possibility of ME/CFS subsets is always there, and a lot more research is needed in order to identify and characterize these subsets.
