Latent viruses as a cause of ME/CFS

SugarSquared said:
Just throwing a question out there, but are there any illnesses caused by latent viruses? It would be useful to be able to compare.
Click to expand...
If you mean illnesses caused while the virus is still in the latent state (not reactivated) then no, there aren't really any recognized examples (that I'm aware of, at least). A couple labs have published papers showing that cells harboring latent virus may have some functional differences since the small amount of viral genes actively transcribed during latency can interact with host proteins. But nobody's really proven a conclusive link between that phenomenon and any disease phenotypes as far as I've heard.
 
Last edited:
MrMagoo said:
I get “fake flu” PEM, I have it now. At times I indulge myself with a Covid test, it’s always negative. I never get to the “fully unwell” point, or temperature. I had come to learn over the years that my body thinks it’s reacting to a virus (and the temperature and sleepiness etc of the flu is all your body trying to kill the virus isn’t it? a virus doesn’t want you to get hot and kill it off)

Not sure I agree with Ron Davis saying it’s “inflammation” though. Is there a basis for that assertion? Is it specifically inflammation, or just general dysfunction?
Click to expand...
Ha! That was the main fun of the first years of Covid for me. Getting PEM that feels ‘that way’ and knowing deep down as I’d felt like that pre covid it wasn’t but just maybe for once it was ‘a virus’
 
jnmaciuch said:
If you mean illnesses caused while the virus is still in the latent state (not reactivated) then no, there aren't really any recognized examples (that I'm aware of, at least). A couple labs have published papers showing that cells harboring latent virus may have some functional differences since the small amount of viral genes actively transcribed during latency can interact with host proteins. But nobody's really proven a conclusive link between that phenomenon and any disease phenotypes.
Click to expand...
This is incorrect. Oral hairy leukoplakia (OHL) is a prime example—a smoldering EBV reactivation that frequently occurs on the tongues of early-stage AIDS patients. It is treated with valaciclovir or famciclovir because both drugs not only target lytic HSV-1, HSV-2, and VZV, but also display solid activity against early abortive-lytic EBV reactivation. I have posted the relevant literature in the thread "Treating ME/CFS with drugs like Valaciclovir/Famciclovir/Truvada that all have activity against early phase EBV reactivation."
 
PageofME said:
This is incorrect. Oral hairy leukoplakia (OHL) is a prime example—a smoldering EBV reactivation that frequently occurs on the tongues of early-stage AIDS patients. It is treated with valaciclovir or famciclovir because both drugs not only target lytic HSV-1, HSV-2, and VZV, but also display solid activity against early abortive-lytic EBV reactivation. I have posted the relevant literature in the thread "Treating ME/CFS with drugs like Valaciclovir/Famciclovir/Truvada that all have activity against early phase EBV reactivation."
Click to expand...
I said in the latent state (not reactivated)
 
Tom Hill said:
I’m brand new to this forum and as a result I’ve only just heard of DecodeME. So the usual accompanying caveats and apologies apply, especially if these thoughts have been thoroughly covered.

I know I’m guilty of sidewalk theorizing here, but I’m really intrigued by the hypothesis (kept alive by the tentative results of the “Pridgen Protocol”) that the multi-systemic cascade of ME/CFS symptoms might be driven by the interactive effect of reactivated HSV and EBV working together. From what I can tell (from really thin scanning of the research on Google), HSV hides itself away in the nervous system, almost entirely in the brain (in the trigeminal ganglion), while EBV hides in the immune system (in B cells, I believe?).

I can’t help joining the dots between what we know about where those two viruses dig in and the findings of DecodeME, which points us strongly in two directions: the nervous system, specifically in the brain, and the immune system.

That ME/CFS would be driven by a complex interactive effect of two dormant/reactivated viruses living in two very different systems would, I imagine, make for a source of the disease that is unusually difficult to pin down through conventional research.

I have no medical research training, so I apologize for blundering around this delicate research landscape like a great Clydesdale busting into an immaculate Hobbit’s kitchen.

I’m just really curious about the theorizing coming out of DecodeMe and what the boffins think are the more promising possibilities.
Click to expand...
I believe the latent/reactivated virus hypothesis in ME/CFS and Long COVID is one of the most promising avenues we have right now. I'm aiming to put together a literature review on this framework and the key active projects as soon as possible.

Much of this frontier work is currently led by US-based teams. Historically, infectiology operated under a rigid dogma: an infection was either fully lytic or completely absent. Because of that older paradigm, many clinicians and researchers from previous generations eventually moved away from the herpesvirus hypothesis in ME/CFS. Naturally, that legacy view still shapes a lot of the general consensus on forums like this, where abortive or localized reactivation isn't yet widely seen as a primary mechanism.

However, a younger generation of researchers—including Liisa Selin (UMass), Maria Ariza (Ohio State), Bhupesh Prusty (Rīga Stradiņš), and Jacqueline Cliff (Brunel)—has been systematically building out this framework. Since the pandemic, leading immunologists new to the field, like Akiko Iwasaki (Yale), alongside excellent younger researchers using novel immunological tools—such as Anayo Kohlgruber (Harvard), and Michela Locci and Mark Painter (UPenn)—have established projects specifically designed to capture abortive-lytic or tissue-specific herpesvirus reactivations that traditional testing misses.

For instance, Selin and Kohlgruber hosted a webinar in April 2026 outlining their findings on T-cell dysregulation in ME/CFS and their ongoing work to identify their precise targets. In May 2026, Painter and Locci presented their findings on T-cells targeting EBV/VZV and impaired B-cells in the lymph nodes during the PolyBio webinar series.

There is a major paradigm shift happening at the research frontier, and I'm looking forward to synthesizing these newer mechanistic models for the community.
 
Last edited:
jnmaciuch said:
I said in the latent state (not reactivated)
Click to expand...
The herpes hypothesis in ME/CFS doesn't claim that the virus causes illness in its purely latent state. There are actually two main hypotheses for how herpesviruses could drive ME/CFS:

  1. Abortive-lytic reactivation: The virus starts the replication process and produces viral proteins, but without finishing full viral particles. The metaphor I use for this is a bakery where dough is constantly being made, but no bread ever gets baked.
  2. Tissue-specific lytic reactivation: The virus is fully active and producing new particles, but the infection is localized to specific deep tissues—for example, limited to the lymph nodes or specific organs—which is why it doesn't show up on standard blood tests and "virus hunters" like Lipkin have never found anything.
 
PageofME said:
The herpes hypothesis in ME/CFS doesn't claim that the virus causes illness in its purely latent state. There are actually two main hypotheses for how herpesviruses could drive ME/CFS:

  1. Abortive-lytic reactivation: The virus starts the replication process and produces viral proteins, but without finishing full viral particles. The metaphor I use for this is a bakery where dough is constantly being made, but no bread ever gets baked.
  2. Tissue-specific lytic reactivation: The virus is fully active and producing new particles, but the infection is localized to specific deep tissues—for example, limited to the lymph nodes or specific organs—which is why it doesn't show up on standard blood tests and "virus hunters" like Lipkin have never found anything.
Click to expand...
I don't think you're following what jnmaciuch said, which was that no viruses are known to cause disease in the latent state. You keep listing effects of reactivated viruses.
 
Creekside said:
I think we already had a discussion about how "inflammation" is commonly misapplied to anything vaguely immune system related. I don't think anyone has found clear evidence of actual inflammation according to the proper definition.
Click to expand...
Yeah that’s what I was thinking, although I did find evidence of it being used as a kind of synonym for dysfunction so I wasn’t sure.

In fact the various uses in medicine probably aids the confusion, even before the unqualified get involved.

Also, look at me doing science!
 
Jonathan Edwards said:
Or cold sores from HSV1, lying latent in epithelium and then replicating to produce sores.
Click to expand...
I thought they infected epithelial cells (allowing transmission between people) but then set up permanent latency in neuronal cell bodies. Then they periodically reactivate from there and travel back down the axon to reinfect the epithelium.
 
OrganicChilli said:
A Google search reveals a photo of a lady who seems to be at least in her 60s.
Click to expand...
To clarify: when I referred to a "younger generation of researchers," I was pointing to the generation of scientists who pursue their research within non-binary models of herpesvirus reactivation—such as abortive-lytic mechanisms. This stands in contrast to the older generation of clinicians and researchers who abandoned the herpes hypothesis altogether because they were thinking strictly within the traditional binary of latent vs. fully lytic replication.

The distinction lies in the scientific paradigm being applied, not in the year of birth.
 
forestglip said:
I don't think you're following what jnmaciuch said, which was that no viruses are known to cause disease in the latent state. You keep listing effects of reactivated viruses.
Click to expand...
I think my reply was adequate. User @jnmaciuch isn't known to me as an expert on herpes research in ME/CFS, but they seem to be bound by the latent-lytic dualism. In my view, that explains why when @SugarSquared asked about the illnesses that herpesviruses cause in the lytic state, @jnmaciuch jumped to explain what they know about illnesses caused by non-reactivating viruses instead.

I'm certainly not an expert on abortive-lytic virus reactivation myself—everything I know about it, I've learned from Maria Ariza's papers.

I would add that these non-binary viral mechanisms aren't just being discussed in ME/CFS anymore—they're increasingly being researched across other complex neurodegenerative and neuroinflammatory illnesses like Multiple Sclerosis and Alzheimer's. In fact, the recent breakthrough linking EBV as a primary trigger for MS has really shifted how people look at persistent herpesvirus activity in the brain and central nervous system.
 
PageofME said:
Yes, Bhupesh Prusty has done it and found EBV and HHV-6 dUTPase in ME/CFS brains.
Click to expand...

We have a thread on that paper.

B

Thread 'Tissue specific signature of HHV-6 infection in ME/CFS, 2022, Prusty et al'

Moved from Research News from Prusty

https://www.frontiersin.org/articles/10.3389/fmolb.2022.1044964/abstract




First exposure to various human herpesviruses (HHVs) including HHV-6, HCMV and EBV does not cause a life-threatening disease. In fact, most individuals are frequently unaware of their first exposure to such pathogens. These herpesviruses acquire lifelong latency in the human body where they show minimal genomic activity required for their survival.

We hypothesized that it is not the latency itself but a timely, regionally restricted...
  • Like


Interesting that nobody thought it worth discussing the data at the time, or when later published. Maybe we should go through it properly.

From what I can see initially the figures are hard to read and confusing. It mentions some controls in a figure legend but I cannot see any pictures for them. The blobs in the ME/CFS pictures don't mean anything to me but I am not familiar with tissue FISH images much.
 
You must log in or register to reply here.
Back
Top Bottom