Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, Paper Pub. 4/1/20 - Dr. Prusty

[raghav]

Unable to read all the study at this moment.
Does Prusty say if others viruses aside from HHV-6 can cause the same problem?

I think he said on Twitter that EBV or CMV too could cause the mitochondrial stuff but wondering if he mentions it in the study.

Yes. Prusty said other viruses also can cause such problems including mito fragmentation. I am quoting from the abstract of his paper
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disorder with many possible triggers. Human herpesvirus (HHV)–6 and HHV-7 are two infectious triggers for which evidence has been growing.

 

[Badpack]

I know its a long shot, but maybe we can contact stealth biotech, the owner of SS31. Im not a native english speaker, so i dont feel that comfortable to do so. Maybe we could ask them, if by any chance, we can get our hands on SS31. Whats your opinion? Here is their eMail: info@stealthbt.com

 

[junkcrap50]

I know its a long shot, but maybe we can contact stealth biotech, the owner of SS31. Im not a native english speaker, so i dont feel that comfortable to do so. Maybe we could ask them, if by any chance, we can get our hands on SS31. Whats your opinion? Here is their eMail: info@stealthbt.com

Better chance to get a peptide lab that synthesizes peptides to manufacture it for "lab use only," hint hint. (note: I'm not condoning it.)

 

[borko2100]

The negative person in question on s4me is ALWAYS negative. I don't recall him having a positive response to any study ever posted on that site. I know there's a lot of bad research out there, but not every single study is a bad one, so I wouldn't take his opinions that seriously.

 

[Badpack]

@junkcrap50 i was looking into that for some time but the problem is they use 40mg daily s.c. in the studies. That would add up to a monthly cost of around $100k if you would purchase it from a lab. Also ignoring that they sell you a powder that somehow you need to portion and liquify it.

 

[MonkeyMan]

@junkcrap50 i was looking into that for some time but the problem is they use 40mg daily s.c. in the studies. That would add up to a monthly cost of around $100k if you would purchase it from a lab. Also ignoring that they sell you a powder that somehow you need to portion and liquify it.

Hi Badpack, I think the only way you could possibly get your hands on the SS31 is if you find a physician who's willing to contact Stealth themselves and ask for some of the drug on compassionate trial basis. Then you would receive the injections, under supervision, in the doctor's office. There are ME/CFS specialists who let their patients try pretty much anything, as long as they sign disclaimers. I once tried micro doses of arsenic trioxide, because my doctor at the time was open-minded enough to let me do that.

 

[Marylib]

I found the new paper from Bupesh to be very interesting in how it kind of ties a few things together that have been floating around. I could be totally misunderstanding this, so bear that in mind.

You have the Dauer response as a reaction to, in this case, an induced HHV6 infection in some cell line or other. So Bupesh posits fragmented mitochondria for the disease mechanism - the "purpose" of this disease mechanism being to keep us alive since the triggering infection didn't kill us in the first place.

But only barely alive, as Mary Schweitzer has put it. As it says in the paper, the body pays a big price for staying alive from the HHV6 infection. It doesby keeping you forever sick - with varying degrees of severity. often for the rest of your life.

It's been known anecdotally for a long time that some PWME don't get colds often - so there is that same mechanism -- fighting like crazy against against a rhinovirus, which most people get fairly often and recover from easily

And Bupesh demonstrated the ability to induce the response in the cells in vitro. Which ties in to looking for something in the blood like Ron Davis and OMF are doing, using the nanoneedle device to measure the induced stress in the cell.

So what is missing in Prusty's paper is, I think, the input of the immunologists? Bupesh is a virus guy - on the infection side of the puzzle?

Now, the Australians come at it from looking at the SNP genetic defect on the calcium ion transport system. They use the clamp device. And they have been able to distinguish samples given by patients diagnosed by strict clinical criteria from other neurological diseases. They are the National Centre for Neuroimmune and Emerging Diseases research group. They have also done something with some unknown dose of naltrexone, only in vitro, which they say is reversing the NK cell degradation - the NK cell thing is by now old and well accepted.

Since Ampligen is still hard to come by - as an immune modulator and anti-viral rolled into one - the Aussies are looking at both a calcium channel blocker and also at the readily available immune modulator called naltrexone in terms of treatment. They have been seeking patients to test naltrexone in whatever the dose they are thinking about, taking their samples in the field also, if necessary.

Jarred Younger is looking at another form of naltrexone altogether for the neuroinflammation But first he has to find a supply.

And then we have stalwart John Chia and his enterovirus samples from stomach tissue. And Klimas and Fletcher looking at gender differences.

So we are basically back to "what disease are we studying and from which angle." And who will get to the finish line first?

So bring on the covid-19 funding for, if any comes, for what may be more cases of post-viral ME from this mutated SARS virus. Who knows yet?

Just my armchair observation.

 

[Badpack]

@Marylib sounds about right, but the thing is, if the fragmented mitochondria are a real problem, we should do everything we can to tread this first. Because whatever the underlining problem is, in the end it doesnt matter if we can tread the result, aka fragmented mitochondria aka low energy levels. And wait for a "real cure" way later down the line while we swinging big with symptomatic therapy.

 

[junkcrap50]

@junkcrap50 i was looking into that for some time but the problem is they use 40mg daily s.c. in the studies. That would add up to a monthly cost of around $100k if you would purchase it from a lab. Also ignoring that they sell you a powder that somehow you need to portion and liquify it.

I found a rough quote of $978/month ($32/dose) for custom synthesized peptide of SS-31(from USA MA). And also found SS31 online $2940/month ($98/dose) but it's from China. Probably cheaper in bulk order. (Still very expensive.)

 

[sb4]

Figured I'd make a separate thread for Prustys paper.

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disorder with many possible triggers. Human herpesvirus (HHV)–6 and HHV-7 are two infectious triggers for which evidence has been growing. To understand possible causative role of HHV-6 in ME/CFS, metabolic and antiviral phenotypes of U2-OS cells were studied with and without chromosomally integrated HHV-6 and with or without virus reactivation using the histone deacetylase inhibitor trichostatin-A. Proteomic analysis was conducted by pulsed stable isotope labeling by amino acids in cell culture analysis. Antiviral properties that were induced by HHV-6 transactivation were studied in virus-naive A549 cells challenged by infection with influenza-A (H1N1) or HSV-1. Mitochondria were fragmented and 1-carbon metabolism, dUTPase, and thymidylate synthase were strongly induced by HHV-6 reactivation, whereas superoxide dismutase 2 and proteins required for mitochondrial oxidation of fatty acid, amino acid, and glucose metabolism, including pyruvate dehydrogenase, were strongly inhibited. Adoptive transfer of U2-OS cell supernatants after reactivation of HHV-6A led to an antiviral state in A549 cells that prevented superinfection with influenza-A and HSV-1. Adoptive transfer of serum from 10 patients with ME/CFS produced a similar fragmentation of mitochondria and the associated antiviral state in the A549 cell assay. In conclusion, HHV-6 reactivation in ME/CFS patients activates a multisystem, proinflammatory, cell danger response that protects against certain RNA and DNA virus infections but comes at the cost of mitochondrial fragmentation and severely compromised energy metabolism.

At one point they show that partially activated HHV6 cause the cell (and surrounding cells?) to enter a state that is very anti viral to other viruses and say that this could be by design from HHV6 point of view. So this would mean that HHV6 put cells in defensive mode in order to stop different viruses from entering it's turf I presume. But wouldn't this make spreading itself to other cells more difficult, unless it doesn't intend to do it and instead just always remain partially active.

Could another interpretation be that it isn't HHV6 deliberately putting cells into defensive mode but the body itself entering this defensive mode because it can sense partial HHV6 activation?

I haven't read the whole paper yet.

 

[Rufous McKinney]

Imagining I can actually follow all this....it will take quite a while to process..

I could see it being adaptive for a virus, to have some ability to take over a resource/niche and then- via some adaptive mechanism, it induces this antiviral state.(in some people)..reducing competition between HHV-6 and other viruses within a given body.

But then I can't explain why I had repeated bouts of Eppstein Barr. How did that virus get in? And all the other v viral illnesses. And the many many times I have been sick with colds, flus.

It is in RECENT YEARS- after say 50 years of this- that I seem to not pick up other flus and colds often- and the fact is: I am very isolated. I was already hiding from germs Nov-March.

****

It also seems possible that one part of the body could be harboring Virus X, and another part is harboring virus Y, and they are hiding out or reactivating in different parts of the body.

 

[wigglethemouse]

Could another interpretation be that it isn't HHV6 deliberately putting cells into defensive mode but the body itself entering this defensive mode because it can sense partial HHV6 activation?

That's kind of the key question. What factor or factors are putting the cells/mitochondria in anti-viral defensive mode, especially in ME/CFS patients. i.e. the "factor in the blood". If he can identify some of those then validation projects and comparison to other diseases will be much more useful, and it might show where the factor is coming from. Identifying those factors is what he is working on now with the money raised by patients.

Interesting to note that Fisher et al's Complex V work used lymphoblasts which are lymphocytes exposed to EBV. His team have used that method on several diseases that show reduced energy function. What they saw different in ME/CFS vs healthy controls vs previous work was unique. But they couldn't identify the cause.

So while anti-viral defense may not necessarily be unique to ME/CFS, can he identify what is making it happen, and where might that signalling factor be coming from? Or perhaps there are subsets, each with a different activating factor........

The door is opening for many more experiments and questions. Funding will be key. Seeing collaboration with Naviaux, an experienced and successful mitochondrial scientist is heart warming.

EDIT : He had a specific experiment in the paper to show cells outside the body when exposed to HHV6 form antiviral defense. He even put only a few HHV6 in the mix to show that most other cells not infected also respond, so cells signal to each other.

 

[Marylib]

Didn't Mary Fletcher, the immunologist, publish a paper about one of the peptides some years ago? All I can remember is something like neuro-peptide Y. But I may have that wrong. Immunology in general is like hieroglyphics to me.
And @Pendergast - what you said makes sense to me, and I did get the joke about CBT.
A healthy friend who is a biochemist in a research unit (not specifically studying this disease alone) thinks people with post-viral ME should all be on anti-retrovirals for the rest of our lives. He says that is where virology is going in general, in terms of how viruses actually replicate, encode themselves in the RNA, and do their dastardly deeds in the human body.

 

[jaybee00]

Don’t contact Stealth. If you, do they will begin to crack down on people who do custom synthesis because they have a patent on ss31 so it will be difficult to get this peptide. This will make things worse, not better.

SS31 is not the only peptide that “work”—some of the the other SS peptides like SS19 peptides also “work”.

 

[drob31]

2 huge key players i see pop up all the time are CDR due to pathogens and the metabolic trap (or both).

 

[raghav]

https://www.immunohorizons.org/cont.../F1.large.jpg?width=800&height=600&carousel=1

What is 3p-hpRNA ? Any idea ? It is the caption of the Orange Vertical bar rightmost in Image D.

 

[wigglethemouse]

What is 3p-hpRNA ? Any idea ? It is the caption of the Orange Vertical bar rightmost in Image D.

It seems to be something to do with H1N1 (the influenza-A virus he used). It can be purchased here. The link seems to suggest it is used to trigger an antiviral immune response.
https://www.invivogen.com/3p-hprna

From text of paper - it was used as a positive control

As a positive control for activation of the viral RNA-sensing pathway and IFN-stimulated gene (ISG) response, cells were transfected with 0.1 ng of 59 triphosphate hairpin RNA (3p-hpRNA) (Invivogen) for 24 h using LyoVec (Invivogen) as a transfection reagent

 

[wigglethemouse]

For anyone wanting to learn more, Dr Bhupesh Prusty covered a lot of whats in the paper at the recent CMRC 2020 conference. He talks rather fast, but it does help understanding of the paper.

 

[heapsreal]

Just read the comments on s4me - awful and so negative. Especially from one person in particular. Talk about kicking you down 🙄 And when asked to explain, told that it would be impossible as we unscientific folk would never understand (paraphrased).... sigh and double sigh!!

I had to look up who this knowledgable 🤔 Dr Was. I wasnt suprised at all to see who it was. The same guy that told everyone to take ibuprofen and stand aside while he and the scientists work it out. Im not quite sure but several years back he thought he could have it all wrapped up in 12 months. That was without ever seeing a cfsme patient. And all previous dr in the field were all on the totally wrong track.

We can say antivirals have a better strike rate then rituximab dribble he was pushing.

 

[jstefl]

I am one who has had great success with Valcyte. I took it for 10 months back in 2008 and have written about my improvements on this site several times. Since then, the cost had dropped considerably.

The improvements have lasted for 12 years and now I am wondering what would have happened if I had continued for a longer period. I attended the HHV 6 foundation conference and listened to Dr. Lerner talk about his experiences with Valcyte. I heard him say that he kept patients on Valcyte until they were cured, with one patient at the time having been on for 7 years.

I am wondering if anybody has experience with low dose Valcyte? It would seem to me that the normal dose is way too strong for long term use and very expensive, even at todays lower prices. I would be happy to hear any stories, good or bad, about this.

I was going through a pile of papers here and found a copy of a patent that Dr. Lerner filed on the use of antivirals for alleviating the symptoms of CFS. It is patent # 6,399,622. It is quite a long document and the pages aren't numbered so I don't know how long. I had forgotten that he had this patent.