EBV & host genetic predispositions increase your risk of MS by 260x and the presence of antibody responses against three or more cross-reactive peptides by up to 1,366x.
From your perspective ('I'me in a corner') re EBV it looks convincing. But there is 'something missing' A very similar presentation can be made for HHV6, another Herpes virus that 'lives' latent and occasionally activating almost exclusively in immune cells. It is inevitable that when there is immune reactivity these viruses are dragged into the events, and appear to be implicated. But are they?......really? There is something else going on 'that is missing' and we must be open to suprises. There must be a case for a serious symposium to thrash out these questions and look for the missing pieces?
If you would like to compare the 'evidence' EBVvs HHV6 you can find data in Lundstrom and Gustafson (Frontiers in Immunology. 2022. and Liebovich and jacobson , Current opinion in virology 2014. But this is not my point. These viruses are latent in immune cells (B in EBV, T cells HHV6 and they must inevitably respond when the immune cells are stimulated. The specifically MS association could well be a red herring. I suspect for other reasons that it is.
Thanks! But I don't really want to miss the main point. Serological and viral genome detection of both EBV and HHV6, are usually significantly detected as raised, not just in MS, but in very many of the 'autoimmune' conditions. Does this mean that EBV etc are the cause of the autoimmunity across the board (a remarkable and VERY important revelation that would demand serious attention! An alternative and much more likely reason is that these viruses are inevitably dragged into the immune processes. The work with Neuromyelitis optica and EBV in revealing. The raised responses to EBV in NMO actually exceed controls and MS, suggesting a non-specific activation. (EBV persistence and reactivation in NMO. Masada S et al J Neurosurgeon Psychi. 2015.) Food for thought.
52% (NMO) vs 25% (MS) (+ 26% HC) is curious indeed. I also wonder if the higher EBV antibody is associated with NMO often being more severe. I have large bright MRI ‘lesions’ along the entire optic pathway of one eye but no diagnosis as yet, so this is personally of some concern but I realize not a query you can answer.
Thanks for your comment. By the way I am in the process of writing a review of the changes in the meningeal membranes and particularly the dura, the tough outer membrane which the MRI people are detecting as being inflamed. Why, many clinicians have asked is the optic tract in MS particularly attacked, and even more strangely, is it nearly always on one side? The attacks on the optic nerve from the circulation in the autoimmune conditions (ADEM, NMO, etc etc) are consistently bilateral. There are strange anatomical peculiarities in MS which may hold the secret!
I can't find the articles you're talking about, could you provide me with the doi?
Doing a literature search, a recent high-quality article (doi: 10.1093/brain/awad418) talks about HHV6 as a possible second hit and admits that the evidence is not remotely comparable to what happens for EBV.
The evidence on the role of EBV in the pathogenesis of MS is overwhelming. Yet studies on antivirals (e.g. tenofovir) in MS are interrupted due to lack of funding. As a doctor I don't like conspiracy theories but I'm starting to be disappointed by the willful blindness of part of the pharmaceutical system
It's difficult for me to comment on this. I have not been tested for anything. I did have a brother that had RRMS, so I had higher odds of getting MS. I always thought MS was either genetical, I lived in the north of England, or because my parents were smokers.
My MS symptoms started after I caught a strain of the herpes virus, although this again was never tested.
Fingers crossed that medical progress is made so that PwMS can lead full lives.
Millions don't get it and a few do. We are all generally exposed to the same stuff. What might do it for one doesn't seem to do it for another predictably, not even identical genes. My mother smoked when Bro and I were in Utero. I got it, he didn't. My cousin got it, her mother (my mom's sister) didn't smoke. My opinion? It's primarily a gene thing which then amplifies influence of environmental factors in certain ways according to which of the 230 genes you have. We need gene tests when born to tell us what we are up against.
The blind men and the elephant is a parable about blind men who all tried to identify an elephant based on touch. One felt the trunk and said it was a snake. Another said the leg was a tree. The tail felt like a rope…
It’s a parable about truth and fallacies, but if you take out the morality question, it’s merely the beginning of a deductive reasoning puzzle. That’s why I say a small child would guess the missing piece—they are not beholden to any past beliefs and can spot things we adults miss.
Whenever I read about the culpability of the EB virus, I wonder about the relevance of all the other factors people seem to blame - eg food, anxiety etc.
I guess all that shows is 'where's there's smoke there's fire'. It doesn't in any way explain a mechanism of action that shows how EBV causes MS. As long as they keep looking at EBNAs, I don't think will lead to a discovery of how it happens. It's over a quarter of a century since Gerlitz and Elroy-Stein noted the similarities between the small non-coding EBV RNA called EBER2 and Adenosine deaminase (https://www.nature.com/articles/2400902 ) and others have followed that line to look at how it interacts with viral gene expression (https://www.nature.com/articles/2400902 ) . If their understanding is right, then EBER2 blocks the degradation of adenosine to inosine. Too much adenosine ain't great. The whole purinergic pathway is affected, and many things flow from that. Looking at EBNAs reminds me of looking at Vitamin D or looking at CCSVI. In the end they were thorough investigations but fruitless. Why not look at EBER2?
In reality, molecular mimicry would explain the mechanism of how EBV causes MS. We just have to wait for these results to be reproduced by other research groups.
Tenovir works by using an analog of the adenosine nucleotide to create chain termination of the EBV DNA chain. Valacyclovir does the same thing but uses an analog of the guanosine nucleotide. Same result with both. I have no doubt at all that EBV is at the root of MS but why keep going over and over the EBNA arguments? There's more going on than just EBNA1.
From your perspective ('I'me in a corner') re EBV it looks convincing. But there is 'something missing' A very similar presentation can be made for HHV6, another Herpes virus that 'lives' latent and occasionally activating almost exclusively in immune cells. It is inevitable that when there is immune reactivity these viruses are dragged into the events, and appear to be implicated. But are they?......really? There is something else going on 'that is missing' and we must be open to suprises. There must be a case for a serious symposium to thrash out these questions and look for the missing pieces?
I wouldn't be so sure that we can reproduce the same results for HHV6 as we did for EBV. Why are you so sure?
If you would like to compare the 'evidence' EBVvs HHV6 you can find data in Lundstrom and Gustafson (Frontiers in Immunology. 2022. and Liebovich and jacobson , Current opinion in virology 2014. But this is not my point. These viruses are latent in immune cells (B in EBV, T cells HHV6 and they must inevitably respond when the immune cells are stimulated. The specifically MS association could well be a red herring. I suspect for other reasons that it is.
These might be the papers Dr Gay refers to: (?)
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.840753/full
https://pmc.ncbi.nlm.nih.gov/articles/PMC4269240/
Thanks! But I don't really want to miss the main point. Serological and viral genome detection of both EBV and HHV6, are usually significantly detected as raised, not just in MS, but in very many of the 'autoimmune' conditions. Does this mean that EBV etc are the cause of the autoimmunity across the board (a remarkable and VERY important revelation that would demand serious attention! An alternative and much more likely reason is that these viruses are inevitably dragged into the immune processes. The work with Neuromyelitis optica and EBV in revealing. The raised responses to EBV in NMO actually exceed controls and MS, suggesting a non-specific activation. (EBV persistence and reactivation in NMO. Masada S et al J Neurosurgeon Psychi. 2015.) Food for thought.
Thanks again Dr Gay for further data,
I now definitely see your point (!) :
52% (NMO) vs 25% (MS) (+ 26% HC) is curious indeed. I also wonder if the higher EBV antibody is associated with NMO often being more severe. I have large bright MRI ‘lesions’ along the entire optic pathway of one eye but no diagnosis as yet, so this is personally of some concern but I realize not a query you can answer.
Thanks for your comment. By the way I am in the process of writing a review of the changes in the meningeal membranes and particularly the dura, the tough outer membrane which the MRI people are detecting as being inflamed. Why, many clinicians have asked is the optic tract in MS particularly attacked, and even more strangely, is it nearly always on one side? The attacks on the optic nerve from the circulation in the autoimmune conditions (ADEM, NMO, etc etc) are consistently bilateral. There are strange anatomical peculiarities in MS which may hold the secret!
I can't find the articles you're talking about, could you provide me with the doi?
Doing a literature search, a recent high-quality article (doi: 10.1093/brain/awad418) talks about HHV6 as a possible second hit and admits that the evidence is not remotely comparable to what happens for EBV.
The evidence on the role of EBV in the pathogenesis of MS is overwhelming. Yet studies on antivirals (e.g. tenofovir) in MS are interrupted due to lack of funding. As a doctor I don't like conspiracy theories but I'm starting to be disappointed by the willful blindness of part of the pharmaceutical system
It's difficult for me to comment on this. I have not been tested for anything. I did have a brother that had RRMS, so I had higher odds of getting MS. I always thought MS was either genetical, I lived in the north of England, or because my parents were smokers.
My MS symptoms started after I caught a strain of the herpes virus, although this again was never tested.
Fingers crossed that medical progress is made so that PwMS can lead full lives.
Xx
Millions don't get it and a few do. We are all generally exposed to the same stuff. What might do it for one doesn't seem to do it for another predictably, not even identical genes. My mother smoked when Bro and I were in Utero. I got it, he didn't. My cousin got it, her mother (my mom's sister) didn't smoke. My opinion? It's primarily a gene thing which then amplifies influence of environmental factors in certain ways according to which of the 230 genes you have. We need gene tests when born to tell us what we are up against.
This feels like the blind men and the elephant. Surely, something dreadfully obvious is missing. Right?
Yep. But what?
I’m sure if we asked small children, they’d know. 😂
Can I ask what you are referring to?
The blind men and the elephant is a parable about blind men who all tried to identify an elephant based on touch. One felt the trunk and said it was a snake. Another said the leg was a tree. The tail felt like a rope…
It’s a parable about truth and fallacies, but if you take out the morality question, it’s merely the beginning of a deductive reasoning puzzle. That’s why I say a small child would guess the missing piece—they are not beholden to any past beliefs and can spot things we adults miss.
Whenever I read about the culpability of the EB virus, I wonder about the relevance of all the other factors people seem to blame - eg food, anxiety etc.
Good morning, thank you for these newsletters, highly appreciated.
Will you be also posting on bluesky soon?
Thank you again.
I guess all that shows is 'where's there's smoke there's fire'. It doesn't in any way explain a mechanism of action that shows how EBV causes MS. As long as they keep looking at EBNAs, I don't think will lead to a discovery of how it happens. It's over a quarter of a century since Gerlitz and Elroy-Stein noted the similarities between the small non-coding EBV RNA called EBER2 and Adenosine deaminase (https://www.nature.com/articles/2400902 ) and others have followed that line to look at how it interacts with viral gene expression (https://www.nature.com/articles/2400902 ) . If their understanding is right, then EBER2 blocks the degradation of adenosine to inosine. Too much adenosine ain't great. The whole purinergic pathway is affected, and many things flow from that. Looking at EBNAs reminds me of looking at Vitamin D or looking at CCSVI. In the end they were thorough investigations but fruitless. Why not look at EBER2?
In reality, molecular mimicry would explain the mechanism of how EBV causes MS. We just have to wait for these results to be reproduced by other research groups.
Tenovir works by using an analog of the adenosine nucleotide to create chain termination of the EBV DNA chain. Valacyclovir does the same thing but uses an analog of the guanosine nucleotide. Same result with both. I have no doubt at all that EBV is at the root of MS but why keep going over and over the EBNA arguments? There's more going on than just EBNA1.