Molecular Mimicry Between Epstein-Barr Virus and Human Herpesvirus-6 Proteins and Central Nervous System Proteins..., 2025, Almulla, Maes et al

[Jonathan Edwards]

BUT. A key part of our overall analysis was that every different autoimmune disease exploits a different 'Achilles heel' in the regulatory 'software'. Some use bypass one way, some another. There are even autoimmune conditions that really are driven by T cell surveillance defects (AIR gene mutations).

And how multiple sclerosis works remains the biggest puzzle. And the role of EBV in all of these things is still not fully understood. Maybe in MS molecular mimicry really does work - but it must work for one specific antigen for a very specific reason. Until we grasp that reason we do not have a helpful theory.

 

[Jonathan Edwards]

The basic message of the 1999 paper was that about fifty diseases might all be cured by cleaning out enough antibody-producing B clones to reset the system to negative feedback for self rather than positive. In practice a few cures occur, in things like ITP. Quite often lethal forms of autoimmune disease like lupus and Wegener's (and vasculitic RA) can be converted to mild manageable versions. Most of the time we end up with a practical way of keeping people very well but getting the system to 'forget' positive feedback proves hard, presumably because we do not get rid of all antibody. It is disappointing to see so little progress on this in 25 years, not just in practical therapeutic terms but in terms of understanding further details of the biology. Most immunologists never seem to have grasped the crucial systems dynamics and the old molecular mimicry theory is still paraded - the 'walking dead' theory.

Sadly Jo is not well and we haven't quite got ME/CFS sussed. But I am beginning to think antibody may be important after all. The question is what new hidden Achilles heel is being exploited if so?
I think it may become clear within a year or two.

 

[Sasha]

getting the system to 'forget' positive feedback proves hard, presumably because we do not get rid of all antibody. It is disappointing to see so little progress on this in 25 years, not just in practical therapeutic terms but in terms of understanding further details of the biology. Most immunologists never seem to have grasped the crucial systems dynamics and the old molecular mimicry theory is still paraded - the 'walking dead' theory.

I want a cure, so how can we start a new school of thought?

I'm sorry to hear Jo isn't well. I'm sure we all appreciate all her hard work for us and hope she feels better soon.

 

[Andy]

Now published,

Molecular Mimicry Between Epstein-Barr Virus and Human Herpesvirus-6 Proteins and Central Nervous System Proteins: Implications for T and B Cell Immunogenicity in an In Silico Study

ABSTRACT

Background

The Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) are frequently linked to neuropsychiatric illnesses such as multiple sclerosis, depression, and chronic fatigue syndrome/myalgic encephalomyelitis. These viruses may induce autoimmune reactions by molecular mimicry, leading to damage to self-epitopes in the central nervous system (CNS).

Objective

This study seeks to explore the common pentapeptides present in EBV and HHV-6 viral antigens alongside various CNS-related proteins via molecular mimicry. Additionally, it will assess the immunogenicity of these shared pentapeptides in T and B cells.

Method

Sequence alignment was conducted to assess molecular mimicry between 32 EBV and HHV-6 antigens and 10 CNS autoantigens. Protein sequences were obtained from UniProt, structural homology was analyzed using AlphaFold and PyMol, and shared pentapeptides were identified with Alignmentaj. Immunogenicity was assessed via the Immune Epitope Database (IEDB) for potential T- and B-cell activation.

Results

A total of 91 mimicry pentapeptides were identified between viral antigens (42 EBV and 49 human HHV-6), and 10 CNS proteins. Notably, synapsin (SYN)1 exhibited the highest mimicry, sharing 13 pentapeptides with (7 with EBV and 6 with HHV-6) viral antigens such as EBV nuclear antigen (EBNA)1, EBNA6, latent membrane protein (LMP)1, and early antigen diffused (EA-D). Myelin proteins, including myelin-associated glycoprotein with 12 shared pentapeptides, myelin basic protein with 9, and myelin-oligodendrocyte glycoprotein with 5, displayed immune cross-reactivity with EBV/HHV-6 antigens. EBNA1, EBNA2, EBNA6, LMP1, LMP2, EA-D, and BLLF1 structurally resemble CNS autoantigens and act as immunoreactive epitopes for human T and B cells. Except for EBNA2 and protein U94, all share immunogenic pentapeptide sequences with SYN1.

Conclusion

Shared pentapeptides suggest a link between viral infections and CNS autoimmunity. Further research is needed to clarify molecular mechanisms and explore targeted therapies to mitigate virus-induced neuroinflammation.

Open access