Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Fluge, Mella et al 2020

I agree that there is quite likely to be an HLA genetic association if we simply assume that an immune mechanism is involved. HLA genes skew responses. But I think an HLA association with a particular virus may not be a good guide. We know that HLA affects susceptibility to specific microbes - we think that is why it is polymorphic. But the two may not be related much. (And I had very mild Covid and yet had LC.)

The paradigm here is post-infective arthritis - perhaps the best documented form of post-infective immune disease. It is linked to HLA-B27 across a wide range of organisms so presumably the B27 risk is not due to presenting any particular peptide. Yet B27 is protective against severity for a number of infections - it is the best way not to get AIDS for years. So the risk factor we know actually partitions severity and risk of post-infective illness. In most cases of post-infective arthritis the triggering infection is mild - often an asymptomatic STD with mild urethritis.

 

Also probably similar in MS. I don't think any good research has been done trying to assess whether the severity of mono is of any relevance, but it appears to be more about an unfortunate sequence of steps where some virions get in the 'right' places where the 'right' conditions allow them to initiate the disease process.

Logically, most likely being locality and proximity to axons. Maybe it's further upstream, about simply getting into some nerve pathways. But it all mostly appears to be chance, unlike AIDS where it's an inevitable final outcome.

 

Thank you all for your insights, tailoring my ideas accordingly