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Excellent Dr John Chia Video Explaining the Mechanism of Enterovirus ME/CFS and Detailing Treatments Like Oxymatrine

Hip

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An excellent video by Dr John Chia from the Invest in ME conference, London 2010, in which he explains the symptoms of acute enterovirus infections, and focuses on the mechanisms by which chronic enterovirus infection may cause ME/CFS. Also details enterovirus ME/CFS treatments like oxymatrine.


This video was previously only available to buy on DVD, but Invest in ME have recently uploaded all their DVD conference videos to their YouTube channel, where they can be viewed for free.

Here are some highlights from the Dr Chia 2010 presentation:
Dr John Chia 2010 Video Highlights


➤ Dr Chia details the symptoms of acute enteroviral infections (timecode 5:15).

➤ Dr Chia mentions giving corticosteroids to a patient with an acute viral infection can be a recipe for disaster, actually causing ME/CFS, because the corticosteroids suppress the immune system and may allow the acute viral infection to get the upper hand (timecode 07:31). There is also a thread on this here.

➤ Dr Chia explains how chronic enteroviral infections can be diagnosed (timecode 10:03).

➤ Dr Chia talks about the enteroviral RNA that was found in the heart, muscles, hypothalamus and brainstem of one ME/CFS patient who was autopsied after her death (timecode 12:34).

➤ Dr Chia says he developed a technique for detecting enteroviruses in ME/CFS patients, which involves taking a stomach biopsy. Dr Chia found enteroviral VP1 protein in ME/CFS patient stomach biopsies, with 82% of ME/CFS patient biopsies being positive for enteroviral VP1 protein, compared to only 20% of healthy controls (timecode 16:03).

➤ Dr Chia discusses the treatment protocols he uses for his ME/CFS patients, and talks about intravenous interferon treatment. However, he says he does not use interferon that much these days, due to high cost, side effects and toxicity (timecode 23:21).

➤ Dr Chia details his treatment protocol using the immunomodulator oxymatrine, which is one of the mainstays of his ME/CFS treatment (timecode 31:28).

➤ Dr Chia explains that he found a shift from the Th2 mode towards Th1 mode in the cytokine profiles of all the ME/CFS patients who responded well to oxymatrine, but that this shift to Th1 was not found in the patients who did not improve on oxymatrine. Th1 is the immune mode needed to fight viral and intracellular infections (timecode 37:05).

➤ Stomach biopsies from ME/CFS patients taken before and after oxymatrine treatment corroborate the idea that the improvements in ME/CFS arise from the immune system fighting off the viral infection. Dr Chia found a reduced presence of enterovirus in the stomach biopsies taken after the oxymatrine treatment, compared to those taken before, indicating that vial loads in the patient are being reduced by oxymatrine (timecode 41:28).

➤ Dr Chia talks about the enterovirus double-stranded RNA (dsRNA) intracellular infections that exist alongside the regular enterovirus infections in ME/CFS patients. Chia says that this dsRNA can open up into its constituent positive and negative strands of single-stranded RNA (ssRNA), and they can multiply inside cells to make more of themselves (timecode 42:39).

➤ Dr Chia talks about the paradox of why there is a persistent enterovirus infection in ME/CFS patients, yet there are so many neutralizing antibodies in the blood that would normally be expected to clear the infection. Dr Chia states that this paradox is explained by the fact that the non-cytolytic enteroviral RNA infection hides inside human cells, and this RNA infection cannot be touched by the neutralizing antibodies that would normally wipe out a viral infection.

Dr Chia says that the body makes interferons which fight the non-cytolytic enteroviral RNA in the cells (and drugs like Ampligen can increase interferon production and thereby ramp up this fight), but this RNA replicates faster than the body's natural interferon is able to wipe it out, so the ME/CFS patient is always losing the battle against the infection.

Dr Chia says, however, that there may be ways to interrupt the non-cytolytic enteroviral RNA replication, and in his opinion, ME/CFS will in the future become be a treatable disease (timecode 43:46).



If you'd like to further explore the chronic non-cytolytic enteroviral RNA infections found in ME/CFS, virologist Prof Nora Chapman provides mechanism of action details on chronic enterovirus in her Invest in ME 2010 presentation. She also provides another good explanation in the Chapman Baltimore 2008 video. But note that the Chapman videos are heavy on virological science.

Dr Chia has given several other very accessible presentations on enteroviruses at Invest in ME London conferences, including his 2009 video, 2011 video and 2015 video. There is also Dr Chia's 2008 Baltimore video. Much of the content of these videos is similar to the content of the above 2010 video.

A PR thread detailing non-cytolytic enteroviruses is found here.

There is an in-depth MEpedia article on non-cytolytic enteroviruses.

There are also MEpedia articles on the enterovirus infections found in the brains of ME/CFS patients, and a history of enterovirus research in ME/CFS (which dates back to British research starting in 1970s, and ends with Dr Chia's pioneering research).
 
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sometexan84

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After watching the video, I'm now more convinced that Enterovirus started it all for me.

I had the sinus issues, then got corticosteroid shots, and had really intense exercise and training regularly. All of which correspond perfectly to what Dr Chia says makes the enterovirus Th2 dominant, causing chronic CFS.

I have a feeling that in 2010 he hadn't yet realized that Oxymatrine does not work on Echovirus 11.

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Hip

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so what could potentially be done about it?
We need to develop drugs or techniques which can wipe out this chronic intracellular infection of non-cytolytic enterovirus dsRNA.

These dsRNA infections are also found inside the cells in other diseases too: for example, in type 1 diabetes, you find enterovirus dsRNA infections in the insulin-producing cells of the pancreas. And Parkinson's has been linked to chronic enterovirus infection of the brain.

So if we could wipe out this enterovirus dsRNA, it may cure not only enterovirus ME/CFS, but other diseases too.



At the moment, oxymatrine is about the only useful treatment on offer for ME/CFS enterovirus dsRNA infections, but this only helps a subset of ME/CFS patients. Some new anti-enterovirus drugs are expected to come out soon, and these may well help.
 

bread.

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We need to develop drugs or techniques which can wipe out this chronic intracellular infection of non-cytolytic enterovirus dsRNA.

These dsRNA infections are also found inside the cells in other diseases too: for example, in type 1 diabetes, you find enterovirus dsRNA infections in the insulin-producing cells of the pancreas. And Parkinson's has been linked to chronic enterovirus infection of the brain.

So if we could wipe out this enterovirus dsRNA, it may cure not only enterovirus ME/CFS, but other diseases too.



At the moment, oxymatrine is about the only useful treatment on offer for ME/CFS enterovirus dsRNA infections, but this only helps a subset of ME/CFS patients. Some new anti-enterovirus drugs are expected to come out soon, and these may well help.
did you try oxymatrine?
 
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Reading this brought up a question I have had for a while. Sorry if I asked you before @Hip but isn't VP1 protein evidence for many different viruses - poliovirus, parvovirus, adenovirus for example? How does Chia associate this with Coxsackie Virus?
 

Hip

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did you try oxymatrine?
I tried oxymatrine multiple times, but unfortunately it did not work for me. It has worked for others on this forum though (see this thread: List of ME/CFS Recovery and Improvement Stories), leading to major improvements in some patients.

Oxymatrine is cheap and available online as a supplement, so pretty straightforward to try it (though it is not advised in those with autoimmune issues, or a family history of autoimmunity).



isn't VP1 protein evidence for many different viruses
I believe enterovirus VP1 protein is only found in enterovirus infections (the enterovirus genus includes coxsackievirus A, coxsackievirus B, echovirus and poliovirus, so all these viruses are detected by VP1 staining).

The VP1 protein stain was a huge breakthrough in enterovirus detection in ME/CFS back in the late 1980s. It was developed by Professor James Mowbray in London.

This VP1 stain is known as the 5-D8/1 monoclonal antibody. It binds to enterovirus VP1 protein and stains enterovirus-infected tissues brown. You can see a picture of this brown stain in enterovirus-infected stomach tissues in this MEpedia article.


There were some issues of the VP1 stain cross-reacting with heart tissues, but a new VP1 stain fixed that issue.
 
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Thanks for the info. I found this quote about 5D8/1
Recently, the broad-spectrum EV antibody 5D8/1 from Dako has been regularly used in both clinical and research settings. This antibody is a mouse monoclonal that recognizes an epitope within the capsid protein P111,19. 5D8/1 mainly identifies EV-B viruses, including CVBs and echoviruses, but also many species A EVs and poliovirus 3 of the C species. However, in non-optimal conditions 5D8/1 has been reported to cross-react with some cellular proteins such as CKB and ATP5B12,15.
Source : https://www.researchgate.net/public...dy_3A6_detects_a_broad_range_of_enteroviruses
 
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There were some issues of the VP1 stain cross-reacting with heart tissues, but a new VP1 stain fixed that issue.
The link leads to a paper on antibody 31A2 raised against CVB3.

This paper states a mix of antibodies would probably be better for diagnostics
The Cox mAB 31A2, which was raised against the VP1 of CVB3, recognizes CVB1 and CVB312 (Laiho et al., submitted), but not other EV serotypes. This narrow recognition pattern of 31A2 needs to be considered when it is used in clinical diagnostics.
As the number of broadly-reactive and serotype-specific EV antibodies expands, the construction of a panel of antibodies that overlap in their ability to bind different EVs the detection of group and serotype specific EV infections will improve. Maccari et al.14 suggested that simultaneous use of 5D8/1 and 9D5 allows for the identification of enterovirus groups based on their differences in their ability to bind to different EVs. Adding 3A6 to this panel, which does not bind to EV-A viruses would make such a test more accurate. Importantly, binding differences could be utilized to construct a multiplexing application based on biosensors to identify a wide range of EV serotypes from liquid samples.
 

Hip

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Enterovirus VP1 staining is not the only means to detect enterovirus infection in the tissues: PCR tests on tissues can be used to detect enteroviral RNA.

Dr Chia's ME/CFS studies on stomach tissue biopsies, as well as all the British ME/CFS studies from the 1990s using skeletal muscle tissue biopsies, found enteroviral RNA in ME/CFS patient tissues via PCR.

Dr Chia has also used PCR to detect the enterovirus dsRNA in the tissues. So that is three different ways to verify enterovirus infection of the tissues in ME/CFS. And of course the forth way is via the chronically elevated enterovirus antibody levels found in ME/CFS, which provide indirect evidence of ongoing enterovirus infection.
 
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In his 2007 paper he used "pan-enterovirus oligodetect kit" which detects a wide range of enterovirus RNA, but it was less senstive than the VP1 test. @Hip has John Chia produced a paper or talk that narrows down the main strains of entereovirus found in patients and the evidence to support that, or is it still non-specific?
 

Hip

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In his 2007 paper he used "pan-enterovirus oligodetect kit" which detects a wide range of enterovirus RNA, but it was less senstive than the VP1 test.
Yes, that is the RT-PCR, which is a sensitive form of PCR. It is less sensitive than the VP1 stain test though.



@Hip has John Chia produced a paper or talk that narrows down the main strains of entereovirus found in patients, or is it still non-specific?
The VP1 stain of tissues is sensitive, but cannot detect individual enterovirus species and enterovirus serotypes. For that you have to use antibody testing. The ARUP lab antibody tests Dr Chia uses detect coxsackievirus B1 to B6, and also detect various echoviruses.

Dr Chia told one patient that the most common enteroviruses he finds in his ME/CFS patients are:
  • CVB3 and CVB4 first and foremost
  • Then CVB2, EV6, EV7 and EV9
  • And then much less EV11
 

sometexan84

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so what could potentially be done about it?
Probiotics
I only just started researching (and treatment with) probiotics. Below are some of my notes regarding specific probiotic bacteria and what they can treat...

Intestinal Permeability ("Leaky Gut") Treatment
I can't say for sure where my enterovirus infections have spread to in my body.

What I do know is A) enterovirus is usually in the GI Tract and Stomach. Usually starts there. B) I have many reasons to suspect an enterovirus infection in my gut. C) I want it to stay there. If it's not too late, I want to make sure I fix any Leaky Gut I have ASAP, because I definitely don't want enterovirus loose in my bloodstream.

And since I believe I do have leaky gut and dysbiosis issues, I'm treating that. I'm doing the Urine - Lactulose & Mannitol Test and the Urine - D-Lactate Test, hopefully next week, which will help diagnose these issues.

Regardless, I'm already starting to treat w/ Probiotics, Magnesium Malate, L-Glutamine, Vitamin D and C, L-Lysine, and my Quercetin arrives on Monday!


Shift from Th2 Dominance
I just started taking LDN (Low-Dose Naltrexone) 2 weeks ago. But LDN helps a lot of things, but can also help reduce Th2 cytokines and restoring balance between Th1 and Th2 lymphocytes. I'm very hopeful for this treatment.

---- EDIT -----


After more research, I am not sure I believe much in the Th1/Th2 Dominance thing. But remember, this info from Dr Chia is 10 yrs old. I still see lots of evidence for LDN helping w/ treatment. I just don't want to lead anyone astray

Antibiotics to help Contain it
I'm also testing for and treating other infections w/ antibiotics, to free up my immune system. For instance, right now, I'm on antibiotics to clear out Streptococcus and Chlamydia Pneumoniae infections. Hopefully this will put less stress on my immune system and free it up a bit so they can focus on other infections like enterovirus, w/out becoming overworked.

That's all I got for now.
 
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I just watched the IIMEC10 2015 presentation.

I'd never heard of 2-3 tender points in the abdomen in a triangular area. That's something I have along with gastritis. No one could ever explain that tender point to me, except one doctor who thought perhaps it was a swollen lymph node.
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In the 2010 video he talks about the importance of boosting the TH1 side of the immune response to address the enterovirus.

Thymosin Alpha 1 is meant to boost antiviral response. @Hip have you looked into whether TA-1 may be useful for enterovirus?
 

Hip

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I only just started researching (and treatment with) probiotics. Below are some of my notes regarding specific probiotic bacteria and what they can treat...
Interesting find. Though note that these are in vitro studies, so they may not necessarily pan out in vivo (often in vitro studies use high doses which cannot be achieved in vivo).

Also, even if there were some antiviral effects in vivo, I would think it will probably only work in the colon, where probiotic bacteria live. Probiotics would not help in the stomach or small intestine, nor any other organs that enterovirus can infect (like the brain, muscles, heart, glands, etc).



I have many reasons to suspect an enterovirus infection in my gut. C) I want it to stay there.
You may be interested to learn that once you have an enterovirus infection of the stomach (which Dr Chia's study found in 82% of ME/CFS patients), it takes only 2 or 3 days for enterovirus to travel along the vagus nerve from stomach to brain, and then enter and infect the brain. That is the case in mouse models, anyway.

Dr Chia mentions this in the Invest in ME Conference 2011 video at 7:28.
 

sometexan84

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Hip

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Thymosin Alpha 1 is meant to boost antiviral response. @Hip have you looked into whether TA-1 may be useful for enterovirus?
The peptides thymosin alpha 1 (Zadaxin) and thymosin beta 4 (TB-500) are prescribed by Dr Kent Holtorf (see page 21 of this document).

I tried thymosin beta 4 a few years back, taking a 2 mg injection once a week for a month or so, but did not notice a great deal. I have an active coxsackievirus B4 infection (high antibody titers of 1:1024).
 

sometexan84

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Interesting find. Though note that these are in vitro studies, so they may not necessarily pan out in vivo (often in vitro studies use high doses which cannot be achieved in vivo).

Also, even if there were some antiviral effects in vivo, I would think it will probably only work in the colon, where probiotic bacteria live. Probiotics would not help in the stomach or small intestine, nor any other organs that enterovirus can infect (like the brain, muscles, heart, glands, etc).
But it could help when deciding on with Probiotics to choose.

And it's really all there is to do for now. Trust me, I've looked! We just don't have much to go on. It's prob best to have some sort of direction, then nothing at all, no?

But again, for me, I am definitely trying to clear and clean out my gut. So if it helps w/ that, then that would be fantastic.

You may be interested to learn that once you have an enterovirus infection of the stomach (which Dr Chia's study found in 82% of ME/CFS patients), it takes only 2 or 3 days for enterovirus to travel along the vagus nerve from stomach to brain, and then enter and infect the brain. That is the case in mouse models, anyway.

Dr Chia mentions this in the Invest in ME Conference 2011 video at 7:28.
I actually am familiar, and it's super scary to me. Which is why I'm being very proactive on that account, looking into testing for meningitis, vagus nerve dysfunction, and trying to get my Serum-based Echovirus IgG titres down.

Seems like if it were that easy for a pathogen to hitch a ride from the stomach to the brain, then we'd all be sick or dead.
 

Hip

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But it could help when deciding on with Probiotics to choose.
Yes, it could do, I guess. Definitely worth trying.



Seems like if it were that easy for a pathogen to hitch a ride from the stomach to the brain, then we'd all be sick or dead.
Perhaps the reason most people do not develop ME/CFS after an enterovirus infection, but a few people do, might simply be down to whether the virus travels along the vagus and into the brain. If you get ME/CFS after an enteroviral infection, maybe that is simply a result of the virus entering your brain. That's a possibility which seems reasonable to me.

There have been very few brain autopsies on deceased ME/CFS patients, but three brain autopsies which were conducted all found enterovirus infection in the brain. See this article.