M.E. caused by enterovirus?

[end]

Judy,
Finally getting back to this. It would be very hard to get to Dr. Chia. I last understood that there was
nothing via *blood tests* that he could "work with" very well. Thought that he HAD to order endoscopy
(?) to be able to diagnose and to treat. Are you saying that he DOES have a way of figuring out
if you have the Coxsackie enterovirus through blood work alone? (I once a year or two called his
office and thought they said the endoscopy was necessary) Are there OTHER
viruses he is looking for other than the standard CFS work up type we have probably
all had ? (Maybe it would be helpful to just know which ones he tests for) If he can figure out if you have it,
my understanding was that there is no way to TREAT it, other than with his Herbs out of China
I think and these have not been very successful from what I heard. Very much appreciate the
information. Maybe reconsider Chia and the effort to go there.

@Raindrop

Blood testing relays specificity but less sensitive, done only via ARUP

Biopsy via endoscopy x4 relays high sensitivity but lacks specificity, VP1 only done via EV Med

 

[halcyon]

I always take antibody tests with a grain of salt because antibodies can cross react. And it looks like that is what happens with the VP1 protein - the antibody that reacts with that also reacts with proteins from 2 mitochondrial enzymes. http://www.ncbi.nlm.nih.gov/pubmed/23335350

So, if you test positive to the VP1, it's not clear if that's the virus or one of those 2 proteins. I'm not sure what cross-reacts with the dsRNA.

First time I tested, I was +ve for dsRNA (2+), -ve for VP!.
Second time I tested, I was the opposite.

It didn't make any sense at all until I learned about the above cross-reactivity. I've lost faith in that test.

The fidelity of the 5D8/1 antibody against VP1 was confirmed in this paper from February. From the paper:

RESULTS:
Clone 5D8/1 labelled CKB, but not ATP5B, on western blots performed under denaturing conditions. In cultured human cell lines, isolated human islets and pancreas sections from patients with type 1 diabetes, the immunolabelling of ATP5B, CKB and VP1 by 5D8/1 was readily distinguishable. Moreover, in a human tissue microarray displaying more than 80 different cells and tissues, only two (stomach and colon; both of which are potential sites of enterovirus infection) were immunopositive when stained with clone 5D8/1.

CONCLUSIONS/INTERPRETATION:
When used under carefully optimised conditions, the immunolabelling pattern detected in sections of human pancreas with clone 5D8/1 did not reflect cross-reactivity with either ATP5B or CKB. Rather, 5D8/1 is likely to be representative of enteroviral antigen expression.

 

[jepps]

This study writes about the mechanism, how coxsackie persists in brain and central nervous system:

Enteroviruses can frequently target the human central nervous system to induce a variety of neurological diseases. Although enteroviruses are highly cytolytic, emerging evidence has shown that these viruses can establish persistent infections both in vivo and in vitro. Here, we investigated the susceptibility of three human brain cell lines, CCF-STTG1, T98G, and SK-N-SH, to infection with three enterovirus serotypes: coxsackievirus B3 (CVB3), enterovirus 71, and coxsackievirus A9. Persistent infection was observed in CVB3-infected CCF-STTG1 cells, as evidenced by prolonged detection of infectious virions, viral RNA, and viral antigens.

Furthermore, proinflammatory chemokines and cytokines, such as vascular cell adhesion molecule 1, interleukin-8 (IL-8), and IL-6, were upregulated in CVB3-infected CCF-STTG1 cells and human progenitor-derived astrocytes. Our data together demonstrate the potential of CCF-STTG1 cells to be a novel cell model for studying CVB3-central nervous system interactions, providing the basis toward a better understanding of CVB3-induced chronic neuropathogenesis.

 

[Hip]

@jepps
To complement that study of coxsackievirus B infected astrocytes in human cell lines, there is also an in vivo study showing that coxsackievirus B infects astrocyte cells in mice brains:

The results showed that coxsackievirus receptor (CAR) was distributed homogeneously on the astrocytes, and that CVB3 could infect and replicate in astrocytes, with release of infectious virus particles. CVB3 induced cytopathic effect and production of proinflammatory cytokines IL-1β, TNF-α, IL-6, and chemokine CXCL10 from astrocytes.

It is particularly interesting that the cytokines IL-1β, TNF-α and IL-6 were released by this coxsackievirus B infection of mouse astrocytes, because Rönnbäck and Hansson have hypothesized that these exact three cytokines may underpin mental fatigue (they are the three main sickness behavior cytokines):

We present the hypothesis that the proinflammatory cytokines tumor necrosis factor-α, IL-1β and IL-6 could be involved in the pathophysiology of mental fatigue through their ability to attenuate the astroglial clearance of extracellular glutamate, their disintegration of the blood brain barrier, and effects on astroglial metabolism and metabolic supply for the neurons, thereby attenuating glutamate transmission.

As well as astrocytes, this study shows coxsackievirus B also seems to be able to chronically infect the neural progenitor cells (stems cells) of the brain.

In terms of how this coxsackievirus B infection manages to persist in the brain and central nervous system, this paper says that that coxsackievirus B may persist in the CNS as a low-level, noncytolytic infection.

 

[jepps]

This has nothing to do with enteroviruses in the brain, but I found it also interesting, as it shows, how coxsackie can result in autoimmunity and inflammatory disease:

http://coolinginflammation.blogspot.co.at/search/label/enterovirus

I examined the enterovirus coat protein, VP1, and found the same three amino acid sequence (three basic amino acids, lysine [K] or arginine [R], highlighted) that I also found in all allergens (peanut, ragweed, dust mite, bee venom) and autoantigens of autoimmune diseases (lupus, MS), and is associated with heparan sulfate-based internalization and presentation of protein immunogens. This observation is consistent with my hypothesis that inflammation plus the presence of one of these proteins, results in production of B and T lymphocytes specific for antigenic determinants on the surface of the immunogen protein. Note that the antigenic determinants usually do not include the three basic amino acid sequence, e.g. RRK, that is involved in uptake and presentation of the protein.

 

[Hip]

@jepps
I also came across that same blog article theorizing how enteroviruses might trigger autoimmunity, and started a thread on it here.

 

[jepps]

Thank you for posting this, sorry, that I did not find this. Time will see, if treating viruses and underlying causes improves our chronic disease. But it is helpful to understand potential relationships. PR is such a good place for this.

 

[Hip]

@jepps
One thing to note is that the chronic inflammatory condition of coxsackievirus B (CVB) myocarditis (heart muscle inflammation) has been classed as autoimmune, but @Jonathan Edwards has pointed out that the inflammation in CVB myocarditis is not true autoimmunity.

I am guessing that chronic CVB myocarditis was perhaps thought of as an autoimmune reaction because, after the initial acute coxsackievirus B infection of the heart, no infectious viral particles can be found in the heart muscle in adult myocarditis (ref: here). Thus there was no explanation as to why the immune system keeps attacking the heart muscle in this chronic inflammatory way.

However, we now know that there appears to be a residue of non-cytolytic enteroviruses left inside the heart muscle cells after the acute CVB infection is over, and it may well be that these non-cytolytic viruses are the cause of the continued heart muscle inflammation: the immune system sees that there is still a virus inside the heart muscle cells, and so keeps attacking them.

Likewise, non-cytolytic enteroviruses living inside the astrocyte cells and neural progenitor cells of the brain may be responsible for the continued brain inflammation found in ME/CFS patients — brain inflammation that may underlie many ME/CFS symptoms.

 

[knackers323]

Yes, what you said @end is right:

The enterovirus antibody tests (micro-neutralization tests) at ARUP Lab (for coxsackievirus B and echovirus) do determine which species of enterovirus you have.

However, this antibody tests are not as sensitive as the enterovirus VP1 protein stain test (aka immunohistochemistry test), which tests a biopsy tissue sample from your stomach for the presence of enteroviruses.

More info about this here:
Enterovirus Foundation

hi @Hip

do you know if the nagalase test is sensitive to enterovirus'?

 

[Dechi]

Anyone familiar with hfme.org? I haven't had a chance to read it all but it is claimed matter of factly that the cause of M.E. is an enterovirus.

Is this known fact? Am I way behind or what?

I have tried looking for contact details on the site to question them on this but cannot find any.

I’m chronically infected with an enterovirus. I started being ill in 2014 and had a gastric biopsy analyzed by Dr Chia 3 years later. It was positive.

 

[perrier]

I’m chronically infected with an enterovirus. I started being ill in 2014 and had a gastric biopsy analyzed by Dr Chia 3 years later. It was positive.

And how are you being treated? Thanks.

 

[Dechi]

And how are you being treated? Thanks.

Well, since there is no treatment any doctor I meet believes in apparently, I am not really treated.

I convinced my doctor to prescribe nimotop, which I’ve been taking for a while, but haven’t been able to get much more. I want to have my blood tested for the type of enterovirus that’s infecting me but I’m having trouble finding someone to help with that.

I seem to be slowly but steadily declining and there isn’t much that I can do about it except rest as much as I can.

My most importwnt battle was to try and get disability. When this is over, maybe I can be more active on being well. Or maybe I’ll be too blasé. Sorry.

 

[knackers323]

@Dechi what were your initial symptoms when you were infected and do you still have all those same symptoms?

 

[Dechi]

@Dechi what were your initial symptoms when you were infected and do you still have all those same symptoms?

I had two separate infections, about 18 months apart. The first one was the worst flu I ever had. I felt so weak I could barely stand up and had to sleep a lot both day and night. It took me about 3 weeks to recover (or so ai thought). After that I would always get the infamous lactic acid feeling in my legs whenever I climbed more than a few stairs. I used to train hard and do weight lifting and sometimes I would almost faint after a workout.

Second infection was like the worst stomach flu. I was very dizzy, could barely stand and walk, felt weak and had severe diarrhea for a few hours. After this one I knew I was never the same. I kept going downhill and had to stop working about six months after the viral infection.

I still have the same symptoms, and many more. Except for diarrhea. My symptoms are variable in intensity depending on how much energy I spend and how much stress I get, but they never completely go away.

 

[knackers323]

@Dechi did dr chia not advise any treatment options?

 

[Hip]

do you know if the nagalase test is sensitive to enterovirus'?

I don't really understand the question. Can you give more details.

 

[Dechi]

@Dechi did dr chia not advise any treatment options?

I’m from Canada so I never saw Dr Chia. My biopsy was sent to him. I tried to get him to give me advice but was told I needed to see him in person or he would not prescribe anything. Maybe I’ll go to California next summer !

 

[knackers323]

I don't really understand the question. Can you give more details.

the nagalase test is apparently an extremely sensitive marker for all cancers and certain viruses, im wondering if enterovirus may be one of them and might be another testing option

its a much easier test to get than the biopsy and micro neutralization test

 

[Hip]

I've never heard of nagalase being connected to enteroviruses.

 

[knackers323]

ive just found online that apparently enterovirus' can effect nagalase levels, but then so can many other things like gut bacteria.

all these tests are very hard to get done, especially if outside the US. might just be easier to try the treatments instead, the few that currently exist anyway