Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in ME/CFS - 2020 - Schreiner

New optical microscopes have become powerful enough to observe mitochondria in real time in 3D and that is bringing new insights. In the past cells had to be fixed to slides and put in an electron microscope to get a good picture, and that process changes the cells.
e.g. https://www.sciencedaily.com/releases/2019/08/190808100336.htm

 

Can't remember if I posted this or not. What's intriguing about the HSV-1 and H1N1 virus challenges in this paper is that renowned virus hunter Dr. Ian Lipkin and team are heading down a similar experimental path in their ME studies.

In Dr. Lipkins talk at the CDC last September he presented the Tru-Culture system from the Institut Pasteur, Paris, that could monitor a virus/bacterial challenge on a patient sample by depressing a plunger at certain time intervals

https://www.youtube.com/watch?v=SViPfk_OGGg

This paper explains the method and how the Tru-culture system compares to conventional PBMC methods
Standardized whole blood stimulation improves immunomonitoring of induced immune responses in multi-center study.

 

https://twitter.com/user/status/1255243194939445251

 

https://twitter.com/user/status/1255261979385761796

https://twitter.com/user/status/1255261986142765057

https://twitter.com/user/status/1255263197495463936

 

Interesting that such study has been done. My muscle biopsy performed within 3 years of onset showed slow-twitch fibre atrophy, which is type 1 and not type 2 as the quoted study found.

Though muscle biopsy is invasive and not that pleasant, in my view we would gain knowledge by studying a cohort of volunteer patients.

 

A user on PR made a very interesting point I think it's worth repeating.

By using a model cell line of A549 cells which are grown in patient or HC serum means means replication of the work is possible. I remember @Jonathan Edwards discussing on the nanoneedle thread after that paper was released that there was no way to replicate that work as the nanoneedle is proprietary. This is very different and it's not complex.

It also allows other researchers to join the hunt for the "something in the blood" molecules, and using model cell lines they can pick apart and analyse what is happening extremely closely.

More researchers can join the hunt which was not possible with the nanoneedle!

 

That's a really good point!

I was thinking that you could avoid the issue of needing the nanoneedle to find the "something in the blood" by replicating Fluge & Mella's study where "cultured human muscle cells indicated that exposure to ME/CFS serum led to increased rates of mitochondrial respiration." Using this you could isolate the "factor" in the serum that causes the the increased mitochondrial respiration and lactate production. I think they used Seahorse equipment to measure the changes. What you provided is definitely another really good approach especially if you want to look into HHV6.

 

I did a good...?!

When I commented asking on his HR blog post, Cort said it was just Naviaux he talked to for that post. Kinda surprised me, as this study seems like Prusty's baby and he's communicative (on Twitter at least). Not sure exactly what aspects Bob contributed to the study? Other than advice on his CDR theory framework...?

I've not really seen detailed discussion of this. (Maybe elsewhere in dedicated threads...?) It seems so revelatory and essential to be thinking about the behavioural states of cells in this kind of way, hammering it out, even if (or especially if) Naviaux hasn't got it all right yet.

I mean, I see a lot of fairly detailed talk (much more than I know or can retain) of what might be directly affecting mitochondria in specific ways and looking closely at them in various contexts. But it seems a little like Lilliputians focusing intently upon a giant's foot, trying to predict how it will move, while failing to think on a grander scale, of the the fact it's attached to a person, who may be seated, walking to the kitchen or laid out dead. Sure if something totally sweeps their feet out from under them, that'll dominate the behaviour. But mostly a top-down theory is essential in systems with so much regulated feedback control. Can't always build up a novel new picture by purely working around the solid edges of the jigsaw puzzle, with only solidly grounded double blind controlled experiments. Although I'll admit the overstated conclusions in the HHV-6 paper did jump out at me, too. Anyway...

The new paper reported seeing SOD2 expression reduced, and smaller mitochondria, so super-oxide (and other ROS) production should be increased, as per Naviaux's Oxidative Shielding [2012]... Yes? And as per point "3)" in section 3 of his [2013] paper on CDR's features.

New paper also effectively reports seeing "5)" in "strongly induced [...] 1-carbon metabolism" (aka 'methylation cycle', right?), so making methyl groups (that can silence genes?; Lipkin mentions seeing hypermethylation in above video, I think). dUTPase and Thymidylate synthase up too, do these promote making DNA instead of RNA, preventing RNA viruses (right?). But I'm totally unclear of wider implications (and mechanistic details)...

Anyway. Prusty describes "M1-proinflammatory form of mitochondria" in this paper, which implies a CDR1 state, from Naviaux's [2018] paper...:



...But Naviaux had ME/CFS as CDR3 illness, there. I wondered if that's why they've not talked about the CDR sub-divisions at all - calling that order into question. Or if that's more because the cancer cells aren't in a normal healthy M2 state to start with? More like M0, with aerobic glycolysis for cell growth...?

Was rambling about this on PR; might they have seen a more notable difference in ATP levels between an M2 and M1 state, than the modest shift actually observed in the cancer cell's hypometabolic shift?

 

You did very good sir! I don't think rules here allow posters to name users on other forums so I kept it anonymous. Until you revealed yourself.

Feel free to include your post on how you interpreted the paper here, if you want to that is, perhaps it will generate further discussion.

And welcome to s4me @ZeroGravitas . This forum was set up to debate and pick apart the science, so while it can seem a bit negative, it's done with good intentions to try to get a better understanding.

 

Well, I sneakily linked it in that quote already [PhoenixRising]. I still have some refinements and additions to edit in, based on (your) comments, etc. May quote paste it here after.

I meant it more as an educational summary, that I didn't think most here would benefit from... Lurked here last year, love the pure science angle, leaving the personal treatments aspect aside, but too intimidated by the obvious bio/medical expertise of most posters. (As a failed physicist & systems engineer with a sieve brain for metabolite names and terminology.) Didn't want to post screens worth of half-knoweledgable speculation/nonsense, as I did with Phair [PhoenixRising]. Or be tempted into a futurism rant about how big data, cheap metabolomics, AI, genetic engineer, etc, will make medicine an exponentially booming information science extension of computing during this decade, finally overhauling our outdated medial practices...

... So yeah:

(1) Anyone any thoughts on CDR1 vs CDR3. Have I failed to understand them or trying to read too much into it, above?

(2) Another question I had in mind for Prusty: do these experiments implicitly give a mechanism for the delay inherent in PEM (24h + ish)?

They cultured the OS-U2 cells for a couple days, to collect the X-factor(s) in the medium. Then cultured the A549 in that medium for a couple more days. Are these time scales *purely* necessitated by the technical requirements of the various analysis they then perform on the cells? Or would it intrinsically take about a day (or few) for a secreted signal to accumulate in the blood to a sufficient concentration? Are sustained levels needed for other cells to react to that. Is there a threshold for cells switching state, rather than an analogue influence (continuos function)?

Naviaux himself has said [2018]:

So, initial reactions can be very fast, but what about the propagated signal...?

 

....Aaand, I killed the thread. May as well stick some nails in the coffin:

Cort just published a nice write-up on a paper from November 2019 by lead author Nuno Sepúlveda [SimmaronResearch]. Full paper text here [NCBI].

"ME/CFS as a Hyper-Regulated Immune System Driven by an Interplay Between Regulatory T Cells and Chronic Human Herpesvirus Infections"

This seems really promising to me, in terms of potential tie-in with this work from Prusty's team. Would it theoretically give a mechanism (and site) for sustained transactivation of HHV-6 (like in their U2-OS cell model)?

Although I see from the previous discussion of this work, in this thread [S4ME], that the supporting clinical data is tenuous (or absent)...?:

I've not read it through, yet (not sure I'll be able to), but this table of information seems quite relevant, here, in describing which cells they think HHV-6 (and the other viruses) infect and then are latent in. Mostly immune cells for HHV-6. Do we think that's vaguely accurate? Given that we know from other work on HHV-6 that it's turned up all over the body, in autopsies, etc:

 

OK, so here's my paper summary previously posted here on the other forum (a couple of tweaks noted):


I think this is the most exciting study since I first came across the hypometabolism (aka dauer) metabolomic studies and Naviaux's Oxidative Shielding, CDR (Cell Danger Response) and Healing Cycle framework, upon which this paper builds!

I'm a decades long gradual onset case, with no obvious acute/infectious events and I've not had colds or flu in many years (hmmm ). So viruses have largely been outside of my self-research interest. Hence I've now been reading up on (and around) this HHV-6 topic since Prusty posted the paper. Minus a few days of frustrating energy crashes, of course. I'll try to summarise my understanding (please correct and question), then do my usual of posting a big list of over-excited questions, later on...

To oversimplify (and and probably overstate) the findings:

ME/CFS is caused by *partial* reactivation of human herpes virus 6 DNA in *some* of our cells, which then send a mystery signalling molecule(s) through our blood that shuts down the rest of our cells.


In more detail:

Prusty et al. demonstrated that human cells (U2-OS), cultured in a lab dish and treated to undergo partial HHV-6 reactivation, secreted a substance into the surrounding medium (supernatant) that, when transferred to a second (responder) culture of separate cells (A549), inhibited cellular energy production.

Serum from each of 10 ME/CFS patients produced the exact same effects! Both also gave the second culture of cells an innate immune resistance to infection from influenza-A (H1N1) and HSV-1 viruses.

They say HHV-6, Human Herpes virus, is found in 90-100% of all humans by age 3. So virtually everyone has it and HHV-7 is very similar. Herpes viruses insert their RNA into the nucleus of human cells, becoming a 'latent' infection, without need to retain viral particles anywhere. But HHV-6 is unique in making its code 'chromosomally integrated', directly part of our own DNA strands. In fact, up to 1% of people are born with inherited HHV-6! Having it in every cell.

They used a drug called TSA (trichostatin-A) that's well known to 'reactivate' HHV-6 in cells they had infected previously. They describe the drug as modelling "genetic and environmental stressors". I think this might equate to the initial acute infectious events, etc, that initiate ME/CFS.

This reactivation didn't go as far as making actual functional virus particles, hence they termed it "transactivation". Only non-structural helper proteins are being made inside of the cells, which are causing metabolic changes and mitochondria to splitting into smaller structures (fission). They found that the most indicative of these proteins is U14, which was also detected in the blood of 40% (8 of 20) patient samples.

They still haven't been able to separate the active (fatigue factor) substance(s) from the transferred cell culture liquid (or ME/CFS serum), in order to identify it. But that seems extremely close at hand, now! Prusty claimed in January that they had a candidate and a couple tests in mind already [previous thread].


Some more notes related to all this:

► The laboratory cells used in the experiments are from cancers. These cell lines are effectively immortal, convenient for standardising lab-work. But they behave a little differently to regular healthy cells, including a strong tenancy towards growth, etc, so exact results aren't proof of behaviour of patient's cell in the body. I.e. ME/CFS patients are not immune to infections, line Covid-19 [Twitter]! The cell lines are:

► U2-OS - Human Bone Osteosarcoma Epithelial Cell, 2T line, established 1964 [microscopyu].
• Their custom U2-OS cells were developed for this 2018 paper [Nature], with latent (chromosomally integrated) ciHHV-6 in the DNA.
• GFP (green fluorescence protein) was integrated into the mitochondrial DNA (for clear visualisation under microscope) of a second batch of U2-OS cells without ciHHV-6 DNA. These were studied after transfer of supernatant from the ciHHV-6 cells, also.

► A549 - Adenocarcinomic human alveolar basal epithelial cells, established 1972 [Wikipedia].
• Chosen to be able to support infection by the test viruses.

[Note: like the majority of human cells, neither cell line can support complete production of HHV-6 virus particles, so are good for studying early stages of reactivation.]


► TSA - histone deacetylase inhibitor trichostatin-A [Wikipedia] - the reactivation trigger which "models Genetic and environmental stressors".
• An antifungal and antibiotic with possible anti-cancer action (via encouraging apoptosis).
• Inhibits the class I and II mammalian histone deacetylase (HDAC) enzyme family [Wikipedia]. Interfering with the removal of acetyl groups, altering gene expression.


► Viral immunity experiment - Comparing effect on (A549) responder cells of being cultured in liquid from (1) trans activated U2-OS cells, (2) ME/CFS patient serum, (3) non-activated U2-OS cells, (4) Control subject serum:




► HHV-6 transactivation's altered enzymes levels in U2-OS cells, (+) = Increased factors, (-) = Decreased, from the paper's abstract:

(+) 1-carbon metabolism - AKA methylation cycle.
(+) dUTPase [Wikipedia] - produces dUMP (precursor of thymidine), decreases dUTP (avoiding uracil's accidental use in DNA in place of thymine) [PhosphoSite]. dUTPases (Udeoxyuridine triphosphate nucleotidohydrolases) are key modulators of innate and adaptive immune responses [NCBI].
(+) Thymidylate synthase - dUMP to dTMP (thymidine monophosphate - DNA nucleotide) [Wikipedia]...

(-) SOD2 (superoxide dismutase 2) - clears reactive oxygen species from mitochonrial energy production. Protects against cell death and inflamatory cytokines.
(-) PDH (pyruvate dehydrogenase) and other proteins required for mitochondrial oxidation of fatty acid, amino acid, and glucose metabolism.

Expressed levels of many mitochondria associated proteins (enzymes) where changed, as measured by pSILAC experiment (pulsed stable isotope labeling by amino acids in cell culture) some significant ones labelled in [Fig1 of paper]:



Note: I think it's only implied that all of these changes in the transactivated cells are transferred via the factor in the cell medium to the second set of cells... Also, I'm not sure how much we should keep in mind that these were cancer cells, with a quite different metabolic resting state that may be affected differently to healthy cells.


► sncRNA-U14 - small noncoding RNA from HHV-6, potent biomarker of recent reactivation, found in 8 of 20 ME/CFS pateint serum (0 of 5 controls). I don't know if it might be present in all ME/CFS cases at below detectable levels [?], but I feel that host cell signals are more likely the main factor (like Naviaux talks about with ATP secretion). List of factors currently being investigated, below...


► Other HHV-6 Viral proteins [Nature] :
• U3-U7 - latency associated.
• U14 - transactivation (early stage - which has been found in many other viruses and bacteria).
• U11 - late stage, needed for making viron (virus particles).
• [Incomplete, could not find a clear list and hard to extract from research papers...]


► Beyond the immediate findings, the setup used is itself a big deal! Giving an alternative to the nano-needle test for detecting the serum factor. Far less practical in an eventual clinical setting, as is, but allowing reproduction in other experimental laboratories. It's also a model for *creating* fatigue factor molecules, in a well known cell line that they can pick apart and analyse extremely closely while its doing it:

"Our mitochondrial reporter-based cell system will provide an opportunity to develop a diagnostic test for ME/CFS as well as provide a platform for further identification of potential factors that define ME/CFS pathophysiology."


► Herpes viruses (all types) establish lifelong infection via many tricks [Wikipedia]. E.g.:

• Producing protein mimicking human interleukin 10 (hIL-10) = cmvIL-10.
Inhibits pro-inflamatory cytokines (IFN-γ, IL-1α, GM-CSF, IL-6 and TNF-α).
• Downregulating MHC I and II (major histocompatibility complex):
- Prevents them presenting viral antigen proteins from inside to cell surface.
- This stops cytotoxic T lymphocytes identifying the infected cell.
• HLA-G upregulated to suppress natural killer cells which usually attack cells not presenting MHCs.


► Roseola [NHS | Wikipedia] body rash following fever is how *initial* HHV-6 (A and B) and HHV-7 infections present in young childhood. Although sometimes asymptomatic, these infections may account for up to ~30% of ER visits for young children with sudden high fever (for up to 5 days).


► Receptor binding for cell entry of virus (and other details), CD = "Cluster of differentiation":
[Note: Prusty's said that the receptors are expressed everywhere (to some extent) so the viruses could access all cells.]

• HHV-6A => CD46 [Wikipedia]
Inhibitory complement receptor (system that enhances antibodies and phagocytic cells).
Also exploited by a strain of measles and group B adenoviruses.

• HHV-6B => CD134 [PubMed | Wikipedia]
AKA "OX40". Part of Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4).
Mostly on CD4 T-Cells.
Activation increases cytokine production.
Associated with pathologic cytokine storm in e.g. H5N1 bird flu.
Activation critical for sustained immune response (past first few days).

• HHV-7 => CD4 (and some cell surface glyoproteins) [Wikipedia]
Enters CD4+ T cells (and macrophages, dendritic cells).
Downregulates CD4 a week after infection (so may interfere with HIV, but reactivaties HHV-6).
95% of adults infected by age 2-5 (generally after HHV-6).
20% show virus in blood, 98% in mouth.


► ME/CFS and HHV-6 on [HHV-6 foundation]: Diagnosis & antiviral treatment; Chromosomally integrated HHV-6 or CIHHV-6; Infecting the brain via the Olfactory (nose) Nerve (affecting Limbic system, Hippocampus); reactivated in transplant patients & under stress; resident in sensory ganglia (per VanElzakker's hypothesis), list of key papers (from researchers e.g. Montoya, Learner, Komaroff, etc).


► Fatigue factor molecule types Prusty has talked about looking for specifically [YouTube]:
• Mitochondrial metabolites (analysing in conjunction with Naviaux).
• Exosomes containing small non-coding RNAs or proteins. Are these the "cryptic peptides" [Twitter]?
• RNA - Cellular or pathogenic (including U14).
• Antibodies - auto (against self), against viruses.
• Calcium flux - altered inside cells so also outside.


List of questions (for researchers or whomever) to follow...

 

Questions asked and replied to on this tweet. Prusty's responses in quotes:

(1) Does time frame of transfer effect suggest mechanism for patient's 1-2 day delayed PEM, crashes, etc? Naviaux's previously said [2018] that "Mitochondria change their function rapidly under stress. Within minutes[...]". But you cultured the HHV-6 transactivated cells for 2 days and then the responder cells for 2 days in the transferred supernatant.

(a) Were these durations necessary for the phenotype transfer to work? (I.e. to accumulate or respond to the molecular factor.) Did you try shorter times to find a minimum?

(b) Or was the duration part of technical requirements of the analysis methods?

(2) Did this paper show cells in a CDR1 state? "M1" mitochondria and anti-viral protection are characteristic of Naviaux's CDR1 state. But he categorises ME/CFS as being a CDR3 disease [2019, Fig.2]:


(a) Was he possibly mistaken about ME/CFS being CDR3 associated?

(b) Or are the majority of our cells stuck in CDR3 as a result of a smaller population of cells in CDR1 (e.g. with HHV-6 transactivation) preventing completion of the healing cycle?

(c) Or are the your observations not sufficient to draw conclusions on this because they are in cancer cells?

(d) Are the lab cancer cells naturally in a proliferative CDR2 state...?


(3) Was Naviaux's contribution to the paper purely advice and/or interpretation (no lab work)?

(4) Which cells in patients are (or aren't) affected?:

(a) Are initial HHV-6A infections mostly limited to cells with higher CD46 expression (chart below)? And HHV-6B to cells with CD134, primarily CD4 T-Cells, etc?

(b) Was HHV-6A virus chosen, instead of 6B or 7, too be able to infect U2-OS and A549

(c) Could the extent of the initial (latent) infection determine the severity of ME/CFS, after the reactivation triggering event has passed?

(d) Or is infection and reactivation in specific locations more likely to be key? E.g. You've found infections all over the brain and brainstem [YouTube].

(e) Could worsening of ME/CFS severity come from a spread of HHV-6 infection to more cells?

(5) Why do most people *not* get ME/CFS after acute infections, surgery, etc? If everyone has HHV-6 (and other viruses) latent in their bodies. (Some factors in 3, genetic and/or metabolic status?)

(6) How does HHV-6 transactivation become chronic in patients?

(a) The U2-OS and A549 cells are incapable of late stage viral replication. Is this also true for some cells in the human body (that can be infected)?

(b) Does the virus deliberately prevent itself from complete replication? What's the evolutionary advantage, if so? Is it related to blocking competing viruses from getting its host cell destroy by the immune system...?

(c) Is another mechanism needed for chronic HHV-6 activation? e.g. another infection, accumulation of toxic elements or other researcher's hypothesis (below)?

(7) Do you suspect interactions with any other proposed mechanisms? I.e. as them causing sustained HHV-6 transactivation, or vice versa? Specifically:

(a) Robert Phair's IDO2 mutation tryptophan trap [2019]?

(b) Nuno Sepúlveda's "Hyper-Regulated Immune System" [2019]?

(c) Michael VanElzakker's "vagus nerve infection" hypothesis [2013]?

(d) Any others you have an eye on...? (E.g. research on ROS/oxidative stress.)



(8) Any hints of patient symptom phenotypes being separable by something you've measured...?:

(a) Detectable U14 (in 40% of sampled patients)?

(b) Inherited ciHHV-6?

(c) What about the never sick patients verses those who catch everything (or at least have repeatedly infection symptops).



(9) ATP production:

(a) Was this shown halved in the U2-OS cells, upon transactivation or with transfered supernatant. But a much more marginal reduction in the A549 cells (am I'm reading the paper right)?

(b) Does [Fig.2D] show halved ATP production purely due to application of TSA? (If so, is that a big distorting factor on results?)

(c) Are the measured ATP concentrations indicate a matching scaling of flux (in production rate)?

(d) Would you expect to see a similar contrast in effect between different tissues within a patient? Or between patients? Or are these results not indicative at all, because they are cancer cells?

(e) Why is there a factor of 10 difference between ATP concentrations graphed in fig.2d verses fig.1c...? (An error?)

(10) Issue with the paper - Does the last sentence of your abstract seems to claim too much? You clearly showed strong similarities but no direct evidence of causation by HHV-6 in patients; it was an in vitro study. Is there unpublished work that bridges this gap?

(11) Serum factor...:

(a) Can you give us any more hints about what molecules you are currently honing in on, or the nature of the tests you've mentioned?

(b) Could the U14 protein be the factor? Seeing as it turns up in so many pathogens. But you only found it in 40% patient serum, so would that make it one of multiple factors? Or could it be pressent in all, but below your detection threshold?

(c) Have you been able to rule out any of the types of molecule you mentioned previously [YouTube]? I.e. Mitochondrial metabolites, exosomes containing small non-coding RNAs or proteins, cellular RNA, antibodies, calcium flux...? And what about purinergic signalling (ATP, etc)?

(12) Personal relevance:

(a) Gradual onset - can this work on latent virus reactivation fit with (very) gradual onset of ME/CFS?

(b) Predisposing factors - could deleterious SNPs of SOD2 (or methylation enzymes, upregulated COMT, etc) make viral activation more likely? Or its effects more pronounced?

(c) Delayed sleep - Could the CDR state (or viral proteins) directly slow down the 24h clock gene expression pattern? Specifically, the astrocytes in the SCN seem to be the body's master time keepers. Because circadian rhythm is so commonly delayed in the illness - probably more of a high level neurological issue (but it was my first symptom, worsening with very gradual onset).

 

(13) General curiosities:

(a) Can HHV-6 DNA show up sometimes in whole genome sequencing? I assume this is deliberately filtered out of the final data, even if its chromosomally integrated...?

(b) How close are we to having a working CRISPR system that could remove HHV-6 from humans (in vivo)? Would have to do this by providing immunity, blacklisting the key viral proteins, or something?

(c) Are there any exciting new laboratory technologies or equipment you expect to have access to in the near future?

(14) So, following on for question 6, incomplete (HHV-6) reactivation is actually the more common, by cell type. Even amongst nucleated cells, the interior is more limiting of viral replication than the surface proteins needed for virus ingress...

(a) Do most cells lack certain molecular machinery/enzymes/gene expression? What is it?

(b) Or are some/most cell types just better at actively suppressing complete replication?

(15) How do anti-virals suppress transactivation (or its effect)? If indeed they do? (Sorry, I've no idea of their mechanisms of action.)

(16) Do you think it could be possible to (quickly) confirm the finding of reduced PDH, SOD2, etc, activity directly in cells taken from patients?

(a) What cell type(s) might be suitable for this, if any? (Keeping in mind the lab methods required, too.)

(b) Or is there little value in this? As you've said, above, that the serum/supernatant factor is all important?

 

McGregor talked about HDAC at the Australia conference in 2019. I believe he also mentioned it as a topic for further research here
https://www.s4me.info/threads/post-...-2019-mcgregor-et-al.10260/page-2#post-181942

I see a new study is going to be looking at gene expression of HDAC
https://www.s4me.info/threads/epige...t-yet-open-for-recruitment.15047/#post-258995

 

Don't think this has been posted yet. I found it very informative.

Note: I'm pretty sure this talk was recorded before Prusty's paper was published so may not include the very latest results but this video helped me understand Prusty's thinking around HHV6/HHV7, mitochondria and ME much better.

Further points of interest:

He's planning a collaboration with other researchers to see if EBV causes similar findings - he hypothesises that all herpes viruses could have the same effect.

He's testing some existing drugs that may prevent the mito fragmentation; says we currently can't fight the actual virus (unless it's actively replicating which mostly it isn't in ME) but treating downstream effects of virus may help symptoms.

He has started analysing donated tissue samples from 6 (?) bodies to see if there are "hidden" herpes infections in e.g. brain tissues - the sort of thing you can't get at when people are alive.

Note: at the start Prusty says a couple of sentences in German but the actual talk is in English. The slides are in German but reasonably self-explanatory. Questions at the end are also in German but with English answers that mostly make sense even without having understood the question.

https://www.youtube.com/watch?v=6jxMbrOwOPg