The viral origin of myalgic encephalomyelitis/chronic fatigue syndrome (Hanson, 2023)

[consuegra]

Amy Proal's position paper on viral persistence in Long Covid.

https://www.nature.com/articles/s41590-023-01601-2#MOESM1

 

[w john martin]

I posted the following comment regarding Dr. Hanson’s article. It refers to research on stealth adapted viruses. I doubt that Dr. Hanson had read any of the referenced articles. Nor do I believe have any readers of Phoenix Rising. CFS communities could, however, assist in their own cause by inquiring to Public Health authorities about these viruses. The published DNA sequence data are irrefutable, although politically awkward. Recognizing the existence of stealth adapted viruses is a key to the therapy of CFS and related illnesses. Kind regards


Stealth Adapted Viruses in CFS Patients

Atypically structured cytopathic viruses have been repeatedly cultured from CFS patients (1,2) The viruses do not normally evoke inflammation due to deletion or mutation of the viral genes coding the relatively few components that are targeted by the cellular immune system. The suffix “itis” in myaglic encephalomyelitis is, therefore, inappropriate, and misleading. The immune evasion mechanism is referred to as stealth adaptation and can potentially occur in all types of viruses, including enteroviruses. Stealth adaptation can also involve the acquisition of additional “renegade” genetic sequences of cellular and microbial origins (3-5). Although their existence has yet to be acknowledged by Public Health officials, the best characterized stealth adapted viruses are derivatives of the cytomegaloviruses infecting the types of monkeys used to produce polio vaccines (3-4).

1. Martin WJ, Zeng LC, Ahmed K, Roy M (1994) Cytomegalovirus-related sequences in an atypical cytopathic virus repeatedly isolated from a patient with the chronic fatigue syndrome. Am J Path. 145: 441-452. PMID: 8053501
2. Martin WJ (1996) Severe stealth virus encephalopathy following chronic fatigue syndrome-like illness: Clinical and histopathological features. Pathobiology 64:1-8. PMID: 8856789
3. Martin WJ (2019) Renegade cellular and/or bacterial genetic sequences in stealth adapted viruses. J Human Virol & Retrovirology 7(2): 26-40. doi: 10.15406/jhvrv.2019.07.00211
4. Martin WJ (2020) Stealth adapted viruses with genetically unstable rhesus monkey cellular sequences. A possible forerunner of complex human illnesses. Cohesive J Microbiol Infect Dis. 4(1). CJMI. 000578. 3(4). doi: 10.31031/CJMI.2020.04.000578
5. Martin WJ (2022) Renegade bacterial genetic sequences in a stealth adapted virus: Biological and diagnostic implications. bioRxiv doi: 10.1101/2022.10.11.511846

 

[consuegra]

I experienced something Eppstein Barr related, since I was a child/many decades ago. But whatever I had was a mild version using criteria, etc. I'd crash, but not in a classic PEM way.

Then something ELSE HAPPENED. I got much worse, over a period of a few months. I feel I'll never know what happened. But did I acquire a new virus?

you would think somebody could at least figure that out. Clearly, there the lack of interest in doing so is remarkable.

Dr. Chia describes that the onset of ME/CFS as he knows it involves several hits on the immune system over a period of time. One too many and you get ME.

Chris

 

[Murph]

COUNTER HANSON
1. In the aftermath of covid and amid the emergence of long covid is a hell of a time to claim that it is enteroviruses not *a group of viruses including coronaviruses* that cause me/cfs. It is certainly possible but it has to be a pretty damn nuanced argument to fly.

PRO HANSON
2. My kids are in childcare. Several times they have caught hand foot and mouth disease (caused an enterovirus that did not exist when I was a little kid but is now endemic. The presentation is a mild runny nose and some spots). Last week For the second time I got the infection, and at the tail end of it felt ABSOLUTELY AMAZING for several days.
Here's where i logged the first time this happened.

I find this to be consistent with a smouldering enterovirus infection. Last time @Hip said a coxsackie vaccine might be very useful for me and I would certainly like to try one when they are made public. (one should be available soon for diabetes, maybe getting it off-label would be possible, idk?)

 

[Violeta]

I posted the following comment regarding Dr. Hanson’s article. It refers to research on stealth adapted viruses. I doubt that Dr. Hanson had read any of the referenced articles. Nor do I believe have any readers of Phoenix Rising. CFS communities could, however, assist in their own cause by inquiring to Public Health authorities about these viruses. The published DNA sequence data are irrefutable, although politically awkward. Recognizing the existence of stealth adapted viruses is a key to the therapy of CFS and related illnesses. Kind regards


Stealth Adapted Viruses in CFS Patients

Atypically structured cytopathic viruses have been repeatedly cultured from CFS patients (1,2) The viruses do not normally evoke inflammation due to deletion or mutation of the viral genes coding the relatively few components that are targeted by the cellular immune system. The suffix “itis” in myaglic encephalomyelitis is, therefore, inappropriate, and misleading. The immune evasion mechanism is referred to as stealth adaptation and can potentially occur in all types of viruses, including enteroviruses. Stealth adaptation can also involve the acquisition of additional “renegade” genetic sequences of cellular and microbial origins (3-5). Although their existence has yet to be acknowledged by Public Health officials, the best characterized stealth adapted viruses are derivatives of the cytomegaloviruses infecting the types of monkeys used to produce polio vaccines (3-4).

1. Martin WJ, Zeng LC, Ahmed K, Roy M (1994) Cytomegalovirus-related sequences in an atypical cytopathic virus repeatedly isolated from a patient with the chronic fatigue syndrome. Am J Path. 145: 441-452. PMID: 8053501
2. Martin WJ (1996) Severe stealth virus encephalopathy following chronic fatigue syndrome-like illness: Clinical and histopathological features. Pathobiology 64:1-8. PMID: 8856789
3. Martin WJ (2019) Renegade cellular and/or bacterial genetic sequences in stealth adapted viruses. J Human Virol & Retrovirology 7(2): 26-40. doi: 10.15406/jhvrv.2019.07.00211
4. Martin WJ (2020) Stealth adapted viruses with genetically unstable rhesus monkey cellular sequences. A possible forerunner of complex human illnesses. Cohesive J Microbiol Infect Dis. 4(1). CJMI. 000578. 3(4). doi: 10.31031/CJMI.2020.04.000578
5. Martin WJ (2022) Renegade bacterial genetic sequences in a stealth adapted virus: Biological and diagnostic implications. bioRxiv doi: 10.1101/2022.10.11.511846

This is very interesting, and at the same time infuriating that it has been overlooked by the public health authorities.

Thank you for all the information, Dr. Martin.

I see that there is a representative from New York that is addressing the need to research and pushing for funding for congenital cytomegalovirus.

I had heard about the issue related to polio vaccine many years ago but then have never seen it discussed. I missed the conversation here, unfortunately, until tonight. My history certainly does match the pattern.

And now I see the virus can exacerbate Sars-Cov-2 infection and subsequent symptoms.


"We show in both endothelial and epithelial cell types that HCMV infection upregulates ACE2, the SARS-CoV-2 cell entry receptor. These observations suggest that HCMV reactivation events in the lung of healthy HCMV carriers could exacerbate SARS-CoV-2 infection and subsequent COVID-19 symptoms."

https://pubmed.ncbi.nlm.nih.gov/364... endothelial,and subsequent COVID-19 symptoms.

 

[w john martin]

Dear Violeta,
Thank you for pointing out the potential interactions between stealth adapted cytomegaloviruses and the SARS-CoV-2 virus. Fortunately, CFS patients are not exceedingly susceptible to severe Covid-19 infections. Stealth adaptation of the SARS-CoV-2 virus remains a distinct possibility and is probably facilitated by the current vaccines (1).

The most intriguing aspect of stealth adaptation is the capacity of the viruses to recombine with cellular and microbial genetic sequences, enabling these sequences to be transmitted between individuals and even between species. This has allowed, for example, the transmission of rhesus monkey cellular sequences to humans (2). It may also explain why many CFS patients test positive for mycoplasma and Lyme disease (3).

Another good reason for Public Health officials to have accepted the existence of stealth adapted viruses is the indication of a non-immunological anti-virus defense mechanism that is mediated by the alternative cellular energy (ACE) pathway (4,5). A better understanding of the ACE pathway would be of benefit to CFS patients.

Martin, W.J. (2021), Stealth adapted coronaviruses resulting from the use of Covid-19 vaccines. The FASEB Journal, 35: doi: 10.1096/fasebj.2021.35.S1.05045​

Martin WJ (2020) Stealth adapted viruses with genetically unstable rhesus monkey cellular sequences. A possible forerunner of complex human illnesses. Cohesive J Microbiol Infect Dis. 4(1). CJMI. 000578. 3(4). doi: 10.31031/CJMI.2020.04.000578​

Martin WJ (2022) Renegade bacterial genetic sequences in a stealth adapted virus: Biological and diagnostic implications. bioRxiv doi: 10.1101/2022.10.11.511846​

Martin WJ. (2016) The ACE pathway in comparison to the immune system in the defense against infectious diseases. J Hum Virol Retrovirol. 4(1):1‒6. doi: 10.15406/jhvrv.2016.04.00124​

Martin WJ (2021) Enhancing the alternative cellular energy (ACE) pathway with KELEA activated water as therapy for infectious diseases. Infectious Disorders – Drug Targets 21(3):314-319. doi: 10.2174/1871526520666200211115111​

​

 

[Violeta]

That would explain why when I had COVID it was not a very severe case. However, since having it a little over a year ago my fatigue is worse. Then my daughter had it last month, and although I didn't get it, I had some symptoms similar to when I had shingles and since then my fatigue is even worse.

Well, that's a little scary about the vaccine causing coronaviruses to go stealth.

I am going to read as much as I can about this today. Thank you for bringing your information to Phoenix Rising and taking the time to answer questions.

 

[Violeta]

This is an interesting study that explains how Human cytomegalovirus (HCMV) can persistently infect humans, but how HCMV avoids humoral immunity.

Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor​

https://www.nature.com/articles/s41467-019-10865-y

 

[Violeta]

Dr Martin, may I ask a question about the ACE pathway.

If I have anything wrong at any point, please feel free to point out errors.

Mainly what I am seeing is that people need ACE inhibitors to lower blood pressure.

Would those with stealth CMV need ACE enhancers? If someone has high blood pressure would the KELEA water make that worse, or is that an erroneous conclusion?

If someone's ACE pathway is obstructed, they would have high levels of bradykinin and that would cause low blood pressure and also elevated vascular permeability. (This seems to be my situation.)

This is me!

Angiotensin II causes the muscular walls of small arteries (arterioles) to constrict (narrow), increasing blood pressure. Angiotensin II also triggers your adrenal glands to release aldosterone and your pituitary gland to release antidiuretic hormone (ADH, or vasopressin).

Lack of Angiotensin II!

One of my first symptoms was related to lack of vasopressin. It started some time around the age of 5 or 6. I had been vaccinated for polio before entering 1st grade. This was in the 50's, so it's possible I had been given a contaminated vaccine. None of my siblings were vaccinated at the same time.

I do have low blood pressure, too.

 

[w john martin]

Dear Violeta,​

It is inevitable that the use of common abbreviations, such as ACE, can lead to misinterpretations as to the intended meaning. I use the term ACE as an abbreviation for a mechanism by which all forms of life can maintain the energy required for normal cellular activities. This mechanism is different from the cellular energy obtained through the metabolism of food and in the case of plants, from photosynthesis. It is more related to what has been called a life force energy, chi, ki, prana, orgone, scalar, etc.​

May I suggest you read the articles: Martin WJ. (2016) The ACE pathway in comparison to the immune system in the defense against infectious diseases. J Hum Virol Retrovirol. 4(1):1‒6. doi: 10.15406/jhvrv.2016.04.00124 and Martin WJ (2021) Enhancing the alternative cellular energy (ACE) pathway with KELEA activated water as therapy for infectious diseases. Infectious Disorders – Drug Targets 21(3):314-319. doi: 10.2174/1871526520666200211115111.​

There is also a book entitled “Stealth Adapted Viruses; Alternative Cellular Energy (ACE) & KELEA Activated Water” which can be obtained in either print form or electronically. Kind regards​

 

[Violeta]

Dear Violeta,​

It is inevitable that the use of common abbreviations, such as ACE, can lead to misinterpretations as to the intended meaning. I use the term ACE as an abbreviation for a mechanism by which all forms of life can maintain the energy required for normal cellular activities. This mechanism is different from the cellular energy obtained through the metabolism of food and in the case of plants, from photosynthesis. It is more related to what has been called a life force energy, chi, ki, prana, orgone, scalar, etc.​

May I suggest you read the articles: Martin WJ. (2016) The ACE pathway in comparison to the immune system in the defense against infectious diseases. J Hum Virol Retrovirol. 4(1):1‒6. doi: 10.15406/jhvrv.2016.04.00124 and Martin WJ (2021) Enhancing the alternative cellular energy (ACE) pathway with KELEA activated water as therapy for infectious diseases. Infectious Disorders – Drug Targets 21(3):314-319. doi: 10.2174/1871526520666200211115111.​

There is also a book entitled “Stealth Adapted Viruses; Alternative Cellular Energy (ACE) & KELEA Activated Water” which can be obtained in either print form or electronically. Kind regards​

Thank you, I am working my way through them.

 

[Atlas]

That rapid and complete switching of states is characteristic of a positive feedback loop. It is not characteristic of chronic infections, permanently degraded cells, microbiome populations, or other hypotheses.

I don't see why a chronic infection could not be a primary perpetuating link in a positive feedback loop.

The chronic infection might not even need be the same as the triggering cause. But the dysfunction triggered by the initial cause could allow a previously under control pathogen already in the body to establish itself and become the primary perpetuating factor in a positive feedback loop.

In this case it's possible that breaking the feedback loop at another point along the line could still result in symptom remission, even if the chronic infection still exists. But the loop would always initiate itself again if left to itself as long as the infection remained.

For example, let's say A is the initial trigger, B is the chronic infection, C, D, E are a feedback loop.


A →
B → C → D → E → C

I find it more likely that the loop from C → C has a strongly amplifying effect on the input from B, but is not completely self sustaining. I.e. without B, it will eventually fizzle out.

In other words the "loop gain" could be positive but less than 1.

If the loop was able to completely sustain itself even with no "fuel on the fire" from B, I would expect to see anyone reaching remission should have permanent remission. Why? Because if the positive feedback chain is broken, the body would supposedly return to normal homeostasis, so there is no reason for the loop to start again without some external factor initiating it again.

 

[unto]

​

​

​

Sorry for the errors, I translate from Italian with Google

I am very convinced that ME is of viral origin 1) because it has historically occurred often as a local epidemic (Los Angeles 1934 London 1950, '55, Lake Tahoe,...... 2) because often in same group (family, friends, work) there have been multiple cases or similar cases,3) historically they have been reported cases of animals (owned by humans suffering from ME) with ME-like symptoms. If you consider the recent Covid19 epidemic where the caseload was very varied; as in ME: there were those who were asymptomatic, some had some mild respiratory symptoms, some gastric symptoms, some had severe pneumonia, animals contracting Covid19 from humans. Then there is Lon-Covid which is very similar to ME, moreover some clinical studies have found the virus alive in various organs many months after infection. 3) From personal experience; May 1985 mild sore throat and sweating between: shoulders, neck, neck (flu-like) then, after 2 months, I start gastric problems, in autumn I start headaches... as the Over the years I have noticed that my family members were showing many symptoms of my ME; finally also friends and partners had (+or-) the same symptoms.

@ w john martin​

I posted the following comment regarding Dr. Hanson’s article. It refers to research on stealth adapted viruses. I doubt that Dr. Hanson had read any of the referenced articles. Nor do I believe have any readers of Phoenix Rising. CFS communities could, however, assist in their own cause by inquiring to Public Health authorities about these viruses. The published DNA sequence data are irrefutable, although politically awkward. Recognizing the existence of stealth adapted viruses is a key to the therapy of CFS and related illnesses. Kind regards

​

I'm happy to see you again Dr. Martin in this forum, I started reading your research around 2003, a few years later I wrote you an e-mail because I was hoping to find a doctor in Italy who believed in ME and his research, but it was useless…. it all started in 1985, I thought about many illnesses, then I saw my family members manifesting them Symptoms of ME, then I saw some people (whom I had exclusively frequented in places other than my house more than 15 years after the onset of ME) who had + or - my symptoms; this is why I am convinced of the viral origin of the Me and when I read about her studies I immediately hoped I had found the solution….. I think that the virus(?) passes mainly through the mouth/nose but then colonizes the intestine and the blood, finally affecting organs such as the heart, kidneys and nerves. I believe an important way to find the cause of ME could be to convince patients that must undergo surgery and have the tissue removed analyzed (by microbiologists who study ME). Greetings

 

[unto]

Patients who are forced to undergo surgery…..

 

[sometexan84]

If ME/CFS were purely a viral persistence issue, you might expect that interferon would make permanent improvements

Why?

I mean, you destroy a bunch of virus, and I guess one could expect (hope) that this portion of virus is now gone for good, resulting in perm improvements. But remember, it's a virus. It's controlled completely, or it's not at all. Viruses have one goal... grow/spread.

and that once interferon reduced viral load, that load would remain low, kept in check by a robust immune response

The virus has created a way to sustain and perpetuate. Interferon treatment won't create a new and perpetual immune initiative against the virus. If IFN treatment doesn't kill it ALL at the root, then the virus will once again take hold.

It's not like bacteria.

But the fact that the virus returns some months after interferon therapy suggests to me that the is some immune weakness or issue that prevents the immune response from keeping these viral infections in check.

100% there's an immune weakness. And if it stems from the viral reservoir in the intestinal epithelium (gut lining), then it's the viral headquarters that need to be annihilated.

Dr Chia's studies (temporarily) cured ME/CFS patients w/ Type I Interferon. Type I Interferon would not be able to destroy the virus in the intestinal epithelium, where it's mostly cells that react to Type III interferon. He destroyed the virus in just about every other place in the body, but not the "headquarters".

There are multiple ways in which a chronic viral presence in the gut lining can cause immune dysregulation (Treg cell alteration, gut microbiome changes, intestinal permeability, etc). The intestinal epithelium is a HUUUUGE regulator of the entire bodies immune system/response.

Destroy it at the root! Virus gone, immune function restored.

 

[Hip]

But remember, it's a virus. It's controlled completely, or it's not at all.

In ME/CFS, you find that the acute lytic enterovirus infection is always controlled. The initial acute infection lasts for a few days, or maybe a few weeks at most, before the immune system brings this lytic infection under full control. Once the lytic infection is under control, you get virtually no new viral particles being made, so that is the end of the acute phase.

But in ME/CFS patients, the immune system does not appear to be able to control non-cytolytic enterovirus, which does not consist of viral particles, but of naked enterovirus RNA living inside cells. The immune system struggles to control it, in spite of the fact that the enteroviral RNA is found at very low levels, and replicates extremely slowly.

You would think that the acute lytic infection would be much harder to fight than the non-cytolytic infection, because during the acute phase, there is a frenzy of new viral particle production, with these new particles going off to infect more cells, and then making even more viral particles inside those cells, in an exponential explosion. Yet the immune system has no trouble bringing this acute infection under full control after some days.

By contrast, during the non-cytolytic chronic phase, viral RNA replication is very slow, and the RNA exists at very low levels. So you would think that the immune system should have a much easier time in bringing this sedate non-cytolytic infection under control. But the fact is, the immune system is incapable of controlling the non-cytolytic infection in ME/CFS patients. Why is this?

Clearly the part of the immune system which deals with lytic infections is working properly; but the part of the immune system which deals with these intracellular non-cytolytic infections seems dysfunctional.



Even when you help the immune system along with interferon therapy (which activates the intracellular immune system to clear non-cytolytic viral RNA), this can temporarily make ME/CFS patients much better as the RNA is cleared; but they relapse again, typically 4 to 12 months after the end of therapy.

The interferon therapy we may assume would have wiped out nearly all of the non-cytolytic infection, which is why the patient feels so much better. But somehow that non-cytolytic infection regrows, causing relapse after 4 to 12 months. The non-cytolytic infection regrows even though it replicates extremely slowly; so in ME/CFS patients, the immune system appears powerless to prevent that regrowth after interferon therapy.

So it seems likely that there is a dysfunction in the intracellular immune response which is responsible for clearing viral RNA from inside cells. This is why the viral RNA can regrow after interferon therapy.

If we could figure out what this dysfunction is, and how to address it, we might cure ME/CFS.

The dysfunction might arise from factors in the body which are throwing a spanner in the workings of the immune system. Such factors could be for example mould or bacterial toxins in the bloodstream which thwart immunity; they could be issues with the autonomic nervous system, which plays an important role in immunity; or any number of things.

IL-10 might be involved in this dysfunction, as this is a key cytokine that facilitates viral persistence.

 

[Hip]

Dr Chia's studies (temporarily) cured ME/CFS patients w/ Type I Interferon. Type I Interferon would not be able to destroy the virus in the intestinal epithelium, where it's mostly cells that react to Type III interferon. He destroyed the virus in just about every other place in the body, but not the "headquarters".

There are multiple ways in which a chronic viral presence in the gut lining can cause immune dysregulation (Treg cell alteration, gut microbiome changes, intestinal permeability, etc). The intestinal epithelium is a HUUUUGE regulator of the entire bodies immune system/response.

Destroy it at the root! Virus gone, immune function restored.

That is an interesting theory, that interferon lambda might cure ME/CFS whereas interferon alpha cannot. It would be great if this proved to be the case.

So far, how long have the improvements in your ME/CFS maintained themselves since you finished your course of interferon lambda? Have the gains maintained themselves, or do you feel you are slowly getting worse again?

 

[heapsreal]

100% there's an immune weakness. And if it stems from the viral reservoir in the intestinal epithelium (gut lining), then it's the viral headquarters that need to be annihilated.

Over 30years of research showing low nk function in cfsme pts which keeps getting ignored. Also, interferon as well as interferon inducing medications increase nk function.

It could be possible to treat EV or other chronic viruses involved, with interferon and then maintain the patient on interferon inducing medication which would support their own interferon production. Although research is lacking on interferon Inducers as the most common known one is immunovir which can definitely be improved upon. Dare I say ampligen, which seems lost in the politics and beaurocrocy of cfsme.

 

[Hip]

It could be possible to treat EV or other chronic viruses involved, with interferon and then maintain the patient on interferon inducing medication which would support their own interferon production.

Yes, these were exactly my thoughts too.

We know that interferon alpha can dramatically improve enterovirus ME/CFS patients (but not herpesvirus patients). But they relapse within a year, likely due to the non-cytolytic enterovirus RNA infection growing back.

But if after interferon therapy you could stimulate the immune system in some way so as to prevent the non-cytolytic infection from regrowing, then the gains in health might be maintained without any relapse.

Stimulating the immune system with further courses of interferon alpha is not a viable solution, as apart from the cost, if you have multiple courses of alpha, then the immune system starts making antibodies that unfortunately target and disable the interferon.

From what I have read, interferon lambda is much less subject to developing such antibodies, so further courses of interferon to maintain remission may be viable.


Interestingly, Dr Chia's observation is that the relapse after interferon therapy often occurs following a heavy bout of prolonged exercise (in one case, the relapse occurred after a week's hiking holiday, where the person was walking many hours each day for several days in a row).

 

[sometexan84]

That is an interesting theory, that interferon lambda might cure ME/CFS whereas interferon alpha cannot. It would be great if this proved to be the case.

So far, how long have the improvements in your ME/CFS maintained themselves since you finished your course of interferon lambda? Have the gains maintained themselves, or do you feel you are slowly getting worse again?

It's maintained. I can still do all the things I couldn't do before and it's not got harder or anything. Got to 85%, and have stayed that way.

I like to think my supplements have helped maintain the progress. But hard to say. So I guess take from that what you will.