The causative link of EBV and MS explained?…ProfG will be happy

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ProfG has been on an EBV crusade, but why or how does it cause/trigger MS?

HLA-DRB1*15:01 is a coreceptor for Epstein-Barr virus, linking genetic and environmental risk factors for multiple sclerosis. Eur J Immunol 2021.

The strongest genetic and environmental risk factors for multiple sclerosis (MS), an inflammatory central nervous system disease, are HLA-DRB1*15:01 and Epstein-Barr virus (EBV). They say

“The mechanisms through which EBV exerts its role in MS are currently unknown”…Are they?

“While it is therefore well known that HLA class II molecules serve as coreceptors for EBV, it was hitherto unknown whether this extends to HLA-DRB1*15:01″…..Is it?

However what does the paper show?.

Should have gone to Spec Savers to get some reading glasses?

However by taking an a B cell line with CD21 that did not express HLA-DR and couldn’t be infected with EBV, they added HLA-DRB1*15.01 and the B cells got infected so they is the genetic link

“This work provides proof of principle that HLA-DRB1*15:01 acts as a coreceptor for EBV on a B cell line. It also evokes the intriguing hypothesis that one mechanism underlying the association of HLA-DRB1*15:01 and MS could be the function of HLA-DRB1*15:01 as a coreceptor for EBV”.

So this study confrims what others have suggested. But how does EV infecting B cells create MS, you can read a hypothesis in one of our papers

Learning from other autoimmunities to understand targeting of B cells to control multiple sclerosis.Baker D, Pryce G, Amor S, Giovannoni G, Schmierer K.Brain. 2018; 141:2834

Anyway another piece in the Jigsaw

CoI I have nothing to do with Spec Savers

Disclaimer: Please note that the opinions expressed here are those of author and do not necessarily reflect the position of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.

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MouseDoctor

13 comments

  • Ya know your mouse model EAE thingie – have you tried infecting the mice with Epstein-Barr virus? Then you could see if they then get the “bad” B cells that target CNS myelin…

    That way you’d end up with a model that more closely matches the disease in humans… or not as the case may be 😉

    • You need to “humanize” the mice by replacing their immune system with human cells as EBV doesn’t infect murine B cells. Its an expensive experiment, as the mice are immunocompromized NOD/SCID, and the uptake repopulation of the human cells takes a few months and likely won’t be 100%. Not that it can’t be done, but you have to have some money and time to throw at it.

    • It was done in germany and presented at ectrims about 3 years ago. but I thing the B cells do not develop properly in the standard mouse

  • If this is the case then there should be no wait for a trial testing better anti virals against EBV. Can start with Tenofovir as its reported here in PNAS that it prevents EBV lytic reactivation

    “Tenofovir prodrugs potently inhibit Epstein–Barr virus lytic DNA replication by targeting the viral DNA polymerase
    Natalia C. Drosu, View ORCID ProfileElazer R. Edelman, and View ORCID ProfileDavid E. Housman”

    https://www.pnas.org/content/117/22/12368

    • “If this is the case then there should be no wait for a trial testing better anti virals against EBV.”

      You’d think so..but

      “speculation until disease activity can be shown to respond to viral inhibition. This may be some way off, as an effective EBV control method has yet to be adequately developed (Cohen, 2018).”

    • I agree antiviral treatments need to get into trials and be developed ASAP. We have over 25 approved disease modifying drugs. It is possible to do it and it is possible to have one approved in the not too distant futur. We also need one capable of crossing the blood brain barrier as well to eliminate all traces of EBV.

  • It’s very good to know that you continue to research and treat MS even in this chaos of Covid-19. This is an encouragement, especially for someone who lives in a country that has Bolsonaro as president trying to kill everyone.

  • There’s more ebv in other disease..than the auto-immune ones you mention.
    EBV in thyroid disease and thyroid cancer…also EBV in aplastic anemia.

    Can EBV cause thyroid nodules?
    Results: The EBV DNA was detected in 71.9% of the samples, and it was also found that the presence of the EBV was associated with increasing development of thyroid tumor. Conclusion: Our results demonstrated that EBV infection may play a role in the development of thyroid tumor.Oct 26, 2018
    https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.27144

    “Because EBV is an autoimmune disease with the hyperfunctioning of T lymphocytes, correlation between EBV infection and the pathogenesis of SAA requires further investigation. Our study preliminarily corroborates the role of EBV in the function of CD8+ T cells in patients with SAA”
    https://www.hindawi.com/journals/bmri/2018/6413815/

  • EBV positivity is not a good marker. Because almost everyone has this. Maybe it is a good anti-marker; if you don’t have it your likelihood of MS is lowered.

    So my first question was “what is the percentage of the population with HLA-DRB1*15:01 ?”

    I found an answer here:
    http://www.allelefrequencies.net/hla6002a.asp?all_name=DRB1*15%3A01

    Hopefully this is a reputable data source. It seems like it varies from a few percent in some population groups up to about 30% in some others. It is not obvious to me by just eyeballing the data that the population groups that have high MS incidence correlate well to this HLA allele. But maybe with closer study some links would be revealed.

    It’s interesting stuff !

    • Its even more confusing than that

      . 40-50% of PWMS do not have HLA-DRB1 15:01

      Slippery fish MS!

  • Mouse doctor if you have the time I would like to know your opinion on the entirety of this research paper as I believe it could very well help explain it in ms.

    Link : https://www.biorxiv.org/content/10.1101/2021.02.02.429395v1.full

    Latent gammaherpesvirus exacerbates arthritis and requires age-associated B cells

    Epstein-Barr virus (EBV) infection is associated with rheumatoid arthritis (RA) in adults, though the nature of the relationship remains unknown. Herein, we examine the contribution of viral infection to the severity of arthritis in mice. We provide the first evidence that latent gammaherpesvirus infection enhances clinical arthritis, modeling EBV’s role in RA. Mice latently infected with a murine analog of EBV, gammaherpesvirus 68 (γHV68), develop more severe collagen-induced arthritis and a Th1-skewed immune profile reminiscent of human disease. We demonstrate that disease enhancement requires viral latency and is not due to active virus stimulation of the immune response. Age-associated B cells (ABCs) are associated with several human autoimmune diseases, including arthritis, though their contribution to disease is not well understood. Using ABC knockout mice, we provide the first evidence that ABCs are mechanistically required for viral enhancement of disease, thereby establishing that latent gammaherpesvirus infection stimulates ABCs to provoke arthritis.

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