Hypothesis Does Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Represent a Poly-Herpesvirus Post-Virus Infectious Disease?, 2025, Ariza et al

[forestglip]

Does Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Represent a Poly-Herpesvirus Post-Virus Infectious Disease?

Ariza, Maria Eugenia; Mena Palomo, Irene; Williams, Marshall V.

[Line breaks added]

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness with unknown etiology. An estimated 17–24 million people representing approximately 1% of the population are afflicted worldwide. In over half of cases, ME/CFS onset is associated with acute “flu-like” symptoms, suggesting a role for viruses.

However, no single virus has been identified as the only etiological agent. This may reflect the approach employed or more strongly the central dogma associated with herpesviruses replication, which states that a herpesvirus exists in two states, either lytic or latent.

The purpose of this review is to address the role that abortive lytic replication may have in the pathogenesis of ME/CFS and other post-acute viral infections and also to raise awareness that these syndromes might be poly-herpesviruses mediated diseases.

Web | DOI | PMC | PDF | Viruses | Open Access

 

[Jonathan Edwards]

Er, no.

 

[forestglip]

An estimated 17–24 million people representing approximately 1% of the population are afflicted worldwide.

I thought that doesn't make sense, since 1% of the world population is around 82 million.

Then I found that this figure has other known issues already. It's apparently based on MS, not ME/CFS. The cited paper is: Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), Eun-Jin Lim et al, Feb 2020

And there was a response to the paper specifically about this 17-24 million people figure:

A global ME/CFS population of 17 to 24 million people is reported in articles such as those published in BMC Medicine [2] and Science [3], all referencing Lim et al. The same range of numbers is also easy to find in patient advocacy websites and news reports, such as those of the American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society [4] and CNN [5], all updated after Lim et al.’s article was published.

However, this figure is drawn from the Background section of Lim et al.’s article, where they state, “In worldwide statistics, approximately 1% of the population, 17 to 24 million people, suffer from this condition [14], which is likely to be as common as rheumatoid arthritis” [1]. The cited reference (reference [14]) is an article about the global burden of multiple sclerosis, and is not relevant to the global ME/CFS population.

Very strange that multiple papers are referencing a figure from the Background section instead of citing the actual result of the paper they're citing, or following the reference from the Background to the actual source for the 24 million figure and citing that (where they'd see it's not even the right condition).

 

[Jonathan Edwards]

The AI crash may hit us by Easter.

 

[ME/CFS Science Blog]

The main theory seems to revolve around the concept of abortive lytic replication, which is explained in these sections:

A central concept regarding the biology of herpesviruses is that two distinct phasesof viral gene expression exist, either latency or lytic replication where virus progeny areproduced. However, there is accumulating data to suggest that in vivo a third state existsin which the virus undergoes abortive lytic replication (ALR). In ALR, the virus initiatesthe lytic cycle but does not fully complete it, resulting in limited viral replication and no production of infectious virions. During this process, some immediate-early and earlylytic genes are expressed, though the specific genes expressed vary across herpesviruses.

Despite evidence of lytic gene activity, the replication process abortsbefore producing infectious virions, thus preventing measurable changes in overall viralburden [76–97].More importantly, although these immediate-early and early genes regulate virusreplication, these same proteins also modulate host genes involved in immune evasion,cell proliferation, the establishment and maintenance of latency, and apoptosis. Elevatedantibodies to the deoxyuridine triphosphate nucleotidohydrolases (dUTPase) encodedby the early genes of EBV (BLLF3), HHV-6 (U45), and VZV (ORF8) were reported inboth longitudinal and single serum samples from patients with ME/CFS compared tocontrols [96,97], suggesting that ALR may be occurring in these patients.

 

[ChronicallyOverIt]

Say this was the issue would IM250 an upcoming herpes virus drug effect this process? It seems like current viral inhibitor herpes drugs have been beat to death with null results

 

[ChronicallyOverIt]

Nvm I read the paper and IM250 would not effect EBV or HHV-6. Also they are saying it’s earlier than the viral replication stage which is what IM-250 stops

 

[PageofME]

IM-250

Thanks for making me aware of the development of Adibelivir. I am an ME/CFS-aciclovir responder. So this sounds intersting to me.

Because of that I am of course very happy about any herpes research into ME/CFS.

I am a still relatively new patient (onset 2017).

Herpes theories have been around for decades and have never been thoroughly researched even though they're the most obvious candidates to look into.

I'd like to encourage patients with flu-like ME/CFS-flares that feel like viral infections to reconsider whether they want to give herpes theories a chance and update themselves on the research and judge for themselves.

In my view there isn't a single hypothesis about ME/CFS pathomechanism that's formulated as clearly and as simply as those of Jacquline Cliff and Bhupesh Prusty and others. And what makes them the leading researchers in the field of ME/CFS is that because of their clear hypotheses they are able to put it to a test.

The empirical tests are the hallmark of good science. Don't listen to anybody who tells you something else.

And right now, nobody else in the ME/CFS field is able to do that.

I think that Carmen Scheibenbogen and Akiko Iwasaki also are trying hard to get they're ideas tested in the field of auto-immune explanations. That's great. However, what they believe ME/CFS is about is a lot more unclear and it will take a lot more time until they can deliver concrete results.

If your ME/CFS flares – or whatever you may call them, your crashes or PEMs – are not flu-like and similar to other herpes infections in symptoms I understand that you think that viral reactivation is not the right explanation for your illness and you're not interested in herpes research.

But you should know that when there's eventually success in the herpes research it will be possible to seperate subgroups rationally and this will help all the other patients as well. Therefore herpes research is a win-win for all the patients.