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Article: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back! 2021, Ariza

Discussion in 'BioMedical ME/CFS Research' started by John Mac, Jan 29, 2021.

  1. John Mac

    John Mac Senior Member (Voting Rights)

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    https://www.mdpi.com/2218-273X/11/2/185
     
    Last edited by a moderator: Jan 29, 2021
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  2. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    Review article.
     
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  3. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    Background : Prof Marshall Williams is the PI on the longstanding NIH grant that is in year 11 studying EBV. The author Maria Eugenia Ariza is the secondary PI on the grant "Stress Effects On Virus Protein Induced Inflammation And Sickness Behavior". The grant has been focused on ME/CFS for a number of years now.
    https://projectreporter.nih.gov/project_info_details.cfm?aid=10049715&icde=31258613
     
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  4. rvallee

    rvallee Senior Member (Voting Rights)

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    Discussion:

    It is clear that the lack of a universally accepted clinical criteria has led to multiple discrepancies, problems and confusion as to how to accurately diagnose and stratify patients with ME/CFS. This has severely hampered the pursue of studies to clearly define the environmental and genetic factors that act as triggers or the downstream mechanisms responsible for the development/progression of ME/CFS. Furthermore, numerous studies using small size patient cohorts, which lack the statistical power to achieve reproducible and rigorous results, have further complicated the task of identifying biomarkers/signatures that would be useful for diagnosing patients.

    The role of some herpesviruses in the development and evolution of ME/CFS in a subset of patients has also been hampered because of the use of classical serological approaches focused primarily on viral proteins expressed during latency or late in the replicative cycle of these viruses or viral load as indicators for the involvement of herpesviruses in the pathobiology of ME/CFS. Recent studies using more advanced serological approaches as well as mechanistic studies have demonstrated the possible role of the EBV BRRF1 and BLLF3 gene products in ME/CFS pathophysiology. Future directions should focus on exploring the use of these gene products for the development of novel therapeutics and/or as biomarkers with diagnostic application or disease progression. Additionally, additional studies need to be performed in light of the new evidence showing high level of abortive lytic replication of these viruses to determine whether other early herpesvirus proteins could contribute to the disease process. Finally, since there is evidence suggesting simultaneous reactivation of multiple herpesviruses in a large percentage of ME/CFS patients, studies should examine whether or not there is cooperative effects between these viruses as well as other viruses within the virome that could contribute to human disease.

    Especially interesting given the last sentence above and how it relates to some areas of current research.
     
    Last edited by a moderator: Feb 6, 2021
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  5. John Mac

    John Mac Senior Member (Voting Rights)

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    News item on their research

    Ohio State researchers isolate biomarker to test for chronic fatigue syndrome
    My bolding
    https://medicine.osu.edu/news/biomarker-for-chronic-fatigue-syndrome
     
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  6. strategist

    strategist Senior Member (Voting Rights)

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    Why is this coming out now?
     
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  7. John Mac

    John Mac Senior Member (Voting Rights)

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    It's just an internal university newspiece about the ongoing work they are doing.
    I don't think the timing of it is of any particular significance.
     
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  8. Mithriel

    Mithriel Senior Member (Voting Rights)

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    EBV has too long an incubation to account for the spread in epidemics and many people are too young to have EBV when they get ill.

    The herpes viruses have been studied in ME for over 30 years. There may be something to learn and they may be important for a lot of people which would be good, but i do wonder if part of the reason for the lack of progress in ME is because enteroviruses are so neglected.
     
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  9. Mij

    Mij Senior Member (Voting Rights)

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    @Mithriel

    How many of us know which virus caused our illness? I had a sudden viral onset (extremely elevated anti-thyroid antibodies), but wasn't tested for any viruses that I'm aware of. I had negative PCR testing for various viruses 10 years later- nothing.

    I'm dealing with frequent viral re-activations since 2002. I'm confused from all the different angles and research as to what is occurring with our immune system.
     
  10. Kitty

    Kitty Senior Member (Voting Rights)

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    I don't think we can, at least in many cases. A lot of common viruses cause a fairly characteristic range of symptoms, but unless a patient is worryingly ill and needs investigations, 'I'm pretty sure it's a virus' often as much as the doctor can say.

    There are even two viruses that cause glandular fever symptoms, so unless you're tested – which is unusual, as diagnosis is often straightforward enough that no tests are needed – you couldn't be sure whether it was caused by EBV or CMV.
     
  11. Mij

    Mij Senior Member (Voting Rights)

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    When I relapsed from taking immune modulators, both HHV6 and EBV reactivated. I experienced a terrible 3 months and recovered, but this was when the OI started.
     
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  12. Wyva

    Wyva Senior Member (Voting Rights)

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    I was actually tested during the infection and later made a habit out of always bringing the test results with me when I see a new doctor, after one once asked in obvious disbelief how I even know that glandular fever started it. (He also happened to tell me it must be neuropsychiatric/neurasthenia.)
     
  13. Mithriel

    Mithriel Senior Member (Voting Rights)

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    I had summer flu which is enteroviral and tested positive for infection a few years later. A lot of viruses have characteristic properties.

    Since basic research has stopped being a priority in medicine viruses have been neglected. Too many are classed as trivial so not worth bothering about like, say coronaviruses :)

    As we know with ME it would be useful if there were simple tests for common viruses. Who knows how many MUS cases have a viral origin and we will never know if no one looks.
     
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  14. Forbin

    Forbin Senior Member (Voting Rights)

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    There was a 2017 paper by Williams, Ariza, et al. that seems to have been a precursor to these findings (Nancy Klimas was also an author on that paper).

    Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology
    Peter Halpin 1, Marshall Vance Williams 1 2, Nancy G Klimas 3 4, Mary Ann Fletcher 3 4, Zachary Barnes 3 5, Maria Eugenia Ariza 1 2

    https://pubmed.ncbi.nlm.nih.gov/28303641/

     
    Last edited by a moderator: Feb 19, 2021
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  15. Milo

    Milo Senior Member (Voting Rights)

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    Thank you @Forbin i remember this paper. I wonder where they are at with their current research and whether this recent reporting is announcing something coming soon.
     
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  16. Hutan

    Hutan Moderator Staff Member

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    Thanks Forbin, I don't think we have a thread for that paper. I'll make one.

    When I have full-on PEM, I'll typically get a cold sore. For 18 months, I had serial cold sores, as in, I always had one, until I was given valacyclovir tablets. Presumably then, the re-activated viruses are producing the dUTPase when my body is not strong enough to keep them under control.

    So, I'm not sure if it's just a down-stream effect that these researchers have identified, and that all sorts of people who aren't in the best of health and who have a latent herpes infection would have higher levels of the dUTPase produced by the herpes viruses.

    Maybe, and I haven't read much yet, but maybe it's a nice test to confirm that a person's immune system isn't doing very well, but it is not necessarily a biomarker.
     
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  17. Hutan

    Hutan Moderator Staff Member

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  18. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    Here are all the papers produced by the authors under the NIH grant.
    https://projectreporter.nih.gov/project_info_results.cfm?aid=10049715&icde=31258613

    The description of this work to uncover biomarkers is covered in the NIH grant project description
    https://projectreporter.nih.gov/project_info_description.cfm?aid=10049715&icde=31258613
     
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  19. Hutan

    Hutan Moderator Staff Member

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    Reference 105: Cox, B.S.; Alharshawi, K.; Lafuse, W.P.; Ariza, M.E. Herpesvirus dUTPases contribute to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome by promoting follicular helper T cell differentiation. JCI 2021. Submitted.

    Potentially relevant to the reported finding of higher numbers of T helper cells in people with ME/CFS (I have had a finding of higher T helper cells).


    There's an awful lot in this review, wrapping up quite a high percentage of current ideas in ME/CFS research, like exosomes, neuroinflammation... Something for everyone. It's beyond me to sift through it and come to a conclusion. It certainly looks as though there is more to come on this, with that follicular helper T cell paper just submitted and the level of enthusiasm in this paper.
     
    Last edited: Feb 19, 2021
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  20. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    Good find @Hutan. Very interesting.
     
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