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Enterovirus Discovery at Stanford--Will a Treatment Follow?

SlamDancin

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@Hip I am neither a disbeliever nor believer in the EV theory. As we’ve discussed before my ARUP panel for Coxsackie and echovirus were largely unremarkable. I have been meaning to ask you for awhile, is it possible that Dr Chia’s success with an Interferon alpha/gamma combo came from the ability of these interferons to stimulate IDO incredibly strongly. From what I’ve read, probably the drugs to induce IDO.
 

Hip

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With the range of potential viral infections and with how little information on how to treat them, I wonder if an empirical approach of trialing some antivirals might make sense.
ME/CFS specialist doctors do give antivirals, and they do help some patients. However, you need to get the blood tests to determine which viruses you have, and then take the appropriate antiviral drugs.



I have been meaning to ask you for awhile, is it possible that Dr Chia’s success with an Interferon alpha/gamma combo came from the ability of these interferons to stimulate IDO incredibly strongly.
I would not have thought so, as there have been 3 studies on interferon therapy for ME/CFS (one of these was Chia's, but there were also studies prior to Chia's work). One of these earlier studies found that interferon only works for enterovirus ME/CFS patients, it does not work if you have other viruses.

Now if interferon were operating via an IDO mechanism, you would expect this would work whether you have enterovirus or another virus. But interferon only works for enterovirus ME/CFS.
 

SlamDancin

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@Hip Seems plausible. Wish they’d do further trials with it.

Another thing I find very interesting and possibly aligning with your GC theory of susceptibility to getting ME is that at least the synthetic GC Dexamethasone has all sorts of effects on both IDO1 and 2, including suppressing IDO1/2 in the periphery when given with LPS. It’s worth a look at I believe;

https://www.ncbi.nlm.nih.gov/m/pubmed/29241670/

LPS-induced Ido1-FL was decreased by DEX in peripheral tissues. In contrast, DEX increased Ido1-v1 expression by astrocytes and microglia, but not peripheral tissues. In comparison, brain Ido2 was minimally induced by LPS or DEX. Uniquely, Ido2-v6 was LPS- and DEX-inducible in astrocytes, suggesting a unique role for astrocytes in response to inflammation and glucocorticoids. Only DEX increased central Tdo2 expression; however, peripheral Tdo2 was upregulated by either LPS or DEX. In summary, specific DO isoforms are increased by LPS and DEX, but LPS-dependent Ido1 and Ido2 induction are attenuated by DEX only in the periphery indicating that elevated DO expression and Kyn production within the brain can occur independent of the periphery.
Keep in mind they were studying this in relationship to depression. It’s not a perfect match but may also explain how low IDO1/2 also allows EV’s into the periphery and eventually somehow into the brain.
 

Hip

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Seems plausible. Wish they’d do further trials with it.
Main problem with interferon therapy is the virus and the ME/CFS symptoms eventually return a few months to a year after the therapy is complete.

You cannot take injected interferon indefinitely to keep the virus at bay like you can an antiviral, because unfortunately the body starts making antibodies which disable the injected interferon. So although injected interferon works very well as an ME/CFS treatment, it's not a viable long term treatment.

However, interestingly enough, interferon taken as a suppository does not lead to antibodies being produced, so this mode of administration could be used indefinitely. I posted some info about interferon suppositories here. Interferon suppositories are also incredibly inexpensive, compared to injectable interferon.

I would like to have tried interferon suppositories as an ME/CFS treatment, but unfortunately Dr Chia found interferon does not work for CVB4 (the virus I have), even though it is effective for CVB3 and CVB5. But if you have B3 or B5, interferon suppositories could be your ticket to much improved health.
 

Hip

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It’s not a perfect match but may also explain how low IDO1/2 also allows EV’s into the periphery and eventually somehow into the brain.
Unfortunately I don't understand enough about IDO1 and IDO2 to make sense of that study.

Interestingly there are several studies (like this one) which show that IDO2 (which in ME/CFS patients is mutated) seems to play an important role in immune tolerance and T-regs, so maybe these IDO2 mutations lead to a dysfunctional way of handling viral infections.
 
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CVB4 is the virus which triggered my ME/CFS. I caught this in 2003, and as this virus spread to over 30 friends and family, it caused a number of illnesses in these people, including sudden heart attacks with myocarditis in the previously healthy. And in one relative who caught my CVB4 while a young boy, he later developed type 1 diabetes as a teenager. My feeling is that he would never had developed T1D if he had not previously caught CVB4, which as you say is linked to T1D.
Same thing happened with me. One of my friends dropped dead while watching his son's hockey game, and another one died in his sleep shortly afterwards (these were guys in their early 30s). A couple of people had weird issues with gallstones, one of them had to have their pancreas removed.
 

Hip

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Same thing happened with me. One of my friends dropped dead while watching his son's hockey game, and another one died in his sleep shortly afterwards (these were guys in their early 30s). A couple of people had weird issues with gallstones, one of them had to have their pancreas removed.
Do you know which virus your ME/CFS is linked to (as indicated by high antibody levels on a blood test)?

You might like this post, where I list all the diseases and medical events that happened to the 30+ friends and family who caught my Coxsackie B4 virus.
 

gbells

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Many viruses trigger nagalase secretion and can contribute to ME due to this however the essential element for chronicity seems to be that some of them must block apoptosis. Without this the body should be able to mount an adaptive immune response and eventually recover. Because enteroviruses don't block apoptosis I am very skeptical that they, in and of themselves, would have a viable mechanism to cause ME.
 
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Do you know which virus your ME/CFS is linked to (as indicated by high antibody levels on a blood test)?

You might like this post, where I list all the diseases and medical events that happened to the 30+ friends and family who caught my Coxsackie B4 virus.
I have had zero positive tests for anything. I haven't been tested for enteroviruses or some of the herpes viruses yet. I'm looking at doing some testing through ARUP labs.

I'll take a look at your post.
 

Hip

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enteroviruses don't block apoptosis
Can you provide a reference for that statement?

Coxsackievirus B has a number of immune evasion mechanisms, including the ability to remove MHC proteins on the surface of the infected cell, which then makes the cell invisible to CD8 T-cell surveillance. Ref: here. So that blocks one mechanism of apoptosis (T-cell triggered apoptosis), though there are also other apoptosis mechanisms.

A protein called 2B made by enterovirus also has anti-apoptotic effects. Ref: here.


And it's not just apoptosis that viruses need to block, but also the interferon response, which fights infections within cells. This paper explains how coxsackievirus B inhibits the type 1 interferon response by producing a protein called 2A.
 

gbells

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Good point on the Calcium depletion however I think it could be overcome by increasing dietary forms of easily absorbable calcium. It definitely would contribute to ME. https://www.ncbi.nlm.nih.gov/pubmed/15680759

I doubt that the interferon effect on antibody triggering of apoptosis would matter if any of the internal apototic pathways are functional since that, in and of itself, would kill the cell.

This is why enterovirus infections are usually short lived. However, I can see them proliferating in cells that are already infected with herpes virus.
 

Hip

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This is why enterovirus infections are usually short lived.
You are not alone in believing that enterovirus can only form short-term infections, even some medical professionals erroneously believe this. The incorrect belief that enterovirus only forms acute but not chronic infections arises from the fact that enterovirus, being an RNA virus, cannot form latent states like DNA viruses can (herpesviruses are DNA viruses). Latency is one of the main (but not only) mechanisms of viral persistence.

But some species of enterovirus, such as coxsackievirus B and echovirus, use another latency-like mechanism to create viral persistence: the chronic infections they create are called non-cytolytic enterovirus. The subject of non-cytolytic enterovirus is complex, and it took me many years to get an understanding of it. Google it if you like.

One study maintained an echovirus infection for 6 years in a cell line, demonstrating that non-cytolytic enterovirus infections are very long lived.

And there are dozens of studies showing chronic enterovirus infections exists in various diseases, such as chronic myocarditis, ME/CFS, Sjogren's, type 1 diabetes, and others.



Good point on the Calcium depletion however I think it could be overcome by increasing dietary forms of easily absorbable calcium.
I think if calcium supplementation were effective against the chronic enterovirus infections found in ME/CFS we would know about it by now!
 

gbells

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The symptoms don't match close enough to be enterovirus. CFS patients don't have most of the enterovirus symptoms including their distinctive rashes.

Symptoms of an enterovirus infection may include:

  • Runny nose, sneezing, cough
  • Sore throat
  • Body and muscle aches
  • Vomiting
  • Fever
  • Conjunctivitis (also known as pink eye or Madras eye)
  • Non-itchy rash on the skin
  • Sores on the mucous membranes, such as blisters inside the mouth
https://www.everydayhealth.com/enterovirus/guide/symptoms/
https://www.dermnetnz.org/topics/enteroviral-infections/
 

Hip

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The symptoms don't match close enough to be enterovirus.
You are looking at the symptoms of enterovirus infection in its acute phase, which is different to the chronic phase.

ME/CFS patients will often display acute enterovirus symptoms when they first catch their virus. For example, coxsackievirus B or echovirus can cause a herpangina sore throat, a flu-like illness or a gastrointestinal illness in the acute phase; and these are symptoms commonly reported by ME/CFS patients when they first catch their virus.

ME/CFS also sometimes appears after mononucleosis, which is usually caused by EBV (but sometimes can be caused by CMV). So if you had mono, and afterwards you developed ME/CFS, your ME/CFS is probably linked to EBV.

But if you had a herpangina sore throat, a flu-like illness or a gastrointestinal illness, and then afterwards developed ME/CFS, that raises suspicion that enterovirus may be the culprit.
 
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gbells

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You are looking at the symptoms of enterovirus infection in its acute phase, which is different to the chronic phase.

ME/CFS patients will often display acute enterovirus symptoms when they first catch their virus. For example, coxsackievirus B or echovirus can cause a herpangina sore throat, a flu-like illness or a gastrointestinal illness in the acute phase; and these are symptoms commonly reported by ME/CFS patients when they first catch their virus.

ME/CFS also sometimes appears after mononucleosis, which is usually caused by EBV (but sometimes can be caused by CMV). So if you had mono, and afterwards you developed ME/CFS, your ME/CFS is probably linked to EBV.

But if you had a herpangina sore throat, a flu-like illness or a gastrointestinal illness, and then afterwards developed ME/CFS, that raises suspicion that enterovirus may be the culprit.
Have any ME patients had improvement treating for enterovirus? What percentage of ME might be due to it?
 

Hip

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Have any ME patients had improvement treating for enterovirus? What percentage of ME might be due to it?
The therapy which really improves enterovirus-associated ME/CFS patients is interferon alpha or beta, which is potently antiviral for enterovirus. Dr Chia has observed bedbound patients going back to work after 2 or 3 months on interferon. Unfortunately they tend to relapse around 4 to 12 months later. This may be because interferon does not fully eliminate the virus from the body, so the virus slowly claws its way back, and ME/CFS returns.

There are several reasons why you cannot keep doing repeat courses of interferon (the cost, the harsh side effects like depression, and the fact that the body eventually makes antibodies which target the injected interferon and disable it, making further interferon ineffective).

So as it stands, interferon therapy does not appear to be the long term cure for enterovirus ME/CFS, but nevertheless dramatically improves patients in the short term, for up to a year.

Although I do wonder whether if an ME/CFS patient were placed on interferon therapy for a year (like they do with hepatitis patients), would that be able to fully eliminate the virus?

Dr Chia does not us interferon much now, because of the relapse issue.


Apart from that, Dr Chia uses the immunomodulator oxymatrine to treat enterovirus ME/CFS. I've seen some people on this forum move up from severe to moderate ME/CFS as a result of oxymatrine. But at least half the time oxymatrine does not help enterovirus ME/CFS patients.

In around a year or so, a potent new anti-enterovirus drug is coming out, which Dr Chia is very hopeful about. I am looking forward to trying that, as I have high antibody titers to coxsackievirus B4, and my ME/CFS started with a herpangina-type sore throat, so that's good evidence that enterovirus is the issue for me.



What percentage of ME might be due to it?
One study by Dr Chia, where he investigated the likely causes of ME/CFS in 200 consecutive patients, concluded that enterovirus is the probable cause in around half of all cases.
 

Dechi

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But in around a year or so, a potent new anti-enterovirus drug is coming out, which Dr Chia is very hopeful about. I am looking forward to trying that, as I have high antibody titers to coxsackievirus B4, and my ME/CFS started with a herpangina-type sore throat, so that's good evidence that enterovirus is the issue for me.
@Hip do you know if this treatment will be available solely through Dr Chia, ie at his office ? I tried to get Oxymatrine but I was told I had to visit his office.