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M.E. caused by enterovirus?

Hip

Senior Member
Messages
17,820
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.

Interesting. I did not know that there was this cross reactivity of the VP1 stain to mitochondrial enzymes.

But you seem to have lost faith for no apparent reason, because the fact that enterovirus RNA is often found at the same time in ME/CFS patients tends to indicate that the VP1 stain picked up enterovirus VP1 protein, and not mitochondrial enzymes.

A similar thing is found in patients with enterovirus myocarditis: both VP1 and the enteroviral RNA are found together in the heart (ref: here)

Plus ME/CFS patients tend to come out positive on the ARUP Lab neutralizing antibodies test.

So these three tests: the VP1 stain, RNA testing, and neutralizing antibodies test all point to enterovirus.

Also, Chia's work with oxymatrine showed that as patients got better on oxymatrine, the amount of VP1 protein in their stomach was markedly reduced (see this video here).

And I believe Chia has found that levels of VP1 and RNA are variable in ME/CFS patients, so it is not unusual to be positive at one time, and negative the next.
 

globalpilot

Senior Member
Messages
626
Location
Ontario
Interesting. I did not know that there was this cross reactivity of the VP1 stain to mitochondrial enzymes.

But you seem to have lost faith for no apparent reason, because the fact that enterovirus RNA is often found at the same time in ME/CFS patients tends to indicate that the VP1 stain picked up enterovirus VP1 protein, and not mitochondrial enzymes.

A similar thing is found in patients with enterovirus myocarditis: both VP1 and the enteroviral RNA are found together in the heart (ref: here)

Plus ME/CFS patients tend to come out positive on the ARUP Lab neutralizing antibodies test.

So these three tests: the VP1 stain, RNA testing, and neutralizing antibodies test all point to enterovirus.

Also, Chia's work with oxymatrine showed that as patients got better on oxymatrine, the amount of VP1 protein in their stomach was markedly reduced (see this video here).

And I believe Chia has found that levels of VP1 and RNA are variable in ME/CFS patients, so it is not unusual to be positive at one time, and negative the next.

Yes, but in my case the dsRNA was not found at the same time. He found no dsRNA when he found the VP1. I also tested for antibodies to all the coxsackie and was negative. I don't know about the other 2 enteroviruses.

I don't know what to think about the dsRNA sometimes being positive and sometimes negative. Where would it go ? It can't just disappear and then return.

Anyway, I'm putting this on the backburner for now. A decent trial of oxymatrine didn't help either.
 

Hip

Senior Member
Messages
17,820
I don't know what to think about the dsRNA sometimes being positive and sometimes negative. Where would it go ? It can't just disappear and then return.

I think a lot depends of what area of the gut is biopsied. The stomach biopsies that Dr Chia has performed take tissue samples at four different sites in the stomach (ref: here), because if you take a sample at just one site in the stomach, you may just miss the infection (the enterovirus infection in stomach tissues is patchy). Even taking samples at four different sites, there is still a chance that all those four site may not happen to have any enterovirus infection in them.

Also, you can imagine that with the ups and downs of ME/CFS, you may have more virus in your body when you are more ill, and less virus when you have perked up a bit.
 
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Hip

Senior Member
Messages
17,820
Another early published paper (1990) from UK researchers is this one:

Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA

This study found that in the cells of ME/CFS patients, there was equal amounts of positive strand and negative strand enteroviral RNA. This is unusual, because normally in an enterovirus infection, you get 100 times more positive strand RNA than negative strand RNA. But in ME/CFS you find equally amounts of positive and negative.

What then happens is that these positive and negative strands of RNA join together to make double stranded RNA (dsRNA). This dsRNA sticks around in human cells as a chronic infection, and this dsRNA is what Dr Chia and other researchers think may be the primary cause of ME/CFS.

This positive and negative strand enteroviral RNA and the dsRNA in the cells is also known as a non-cytopathic or non-cytolytic enterovirus infection.
 
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globalpilot

Senior Member
Messages
626
Location
Ontario
I had 3 sites tested Hip. I can't just keep getting endoscopies to get more biopsy samples so that I may finally test positive. I just can't accept that it is this difficult.

I wish I had up and downs! I'm nice and stable at a 1.5-2 out of 10.
 

Hip

Senior Member
Messages
17,820
@globalpilot
The thing is, I should think that enterovirus infections of the stomach per se will not cause ME/CFS. These stomach infection are probably no more than an indicator you have a chronic enterovirus infection going on.

My guess is that you only get ME/CFS if enterovirus enters the brain or nervous system. In an autopsy of an ME/CFS patient, enterovirus RNA was found in the brainstem and hypothalamus (ref: here).

Unfortunately there is no way to take brain or nervous system biopsies in living ME/CFS patients, only at autopsy. But if you could test the brain this way, I suspect that all enterovirus-associated ME/CFS patients would show strong infections in the brain and nervous system.


It is of course possible that your ME/CFS does not arise from an enterovirus infection. For example, there are a number of known causes of ME/CFS: parvovirus B19, Chlamydia pneumoniae, Coxiella burnetii and Giardia lamblia can all cause ME/CFS. It could be that your ME/CFS is caused by one of these.
 

Hip

Senior Member
Messages
17,820
Incidentally, I have recently been re-reading the research related to the problems ME/CFS patients have with their RNase L.

In response to interferon, human cells release this antiviral compound called RNase L. It is the function of RNase L to destroy singled stranded viral RNA within our cells.

However, in ME/CFS patients, the RNase L has been cut up into small pieces, so it no longer works properly, and it is believed this is one reason why we cannot easily clear out the enteroviral RNA infection from our cells.
 
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globalpilot

Senior Member
Messages
626
Location
Ontario
@globalpilot

It is of course possible that your ME/CFS does not arise from an enterovirus infection. For example, there are a number of known causes of ME/CFS: parvovirus B19, Chlamydia pneumoniae, Coxiella burnetii and Giardia lamblia can all cause ME/CFS. It could be that your ME/CFS is caused by one of these.

Yes, enterovirus isn't the only thing I'm considering.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Let me clarify something. There are NO known causes of ME. There are known triggering events, that is initial infections or injury. We do not know, for sure, than any are causal, though I think a strong case might be made they are co-causal. While many were ruled out over the decades, now we know the bases on which they were ruled out relied on flawed scientific interpretations, largely due to the immaturity of the science. Hence many are back in, and herpes and enteroviruses are back in with a vengeance.

However there was a paper published a few back that showed that all (most?) of the infections associated with ME or CFS have a similar lifecycle, with similar tissue tropisms (that is they infect similar tissues). I do not think that is coincidence. In particular they all affect the gut, and can exist inside B cells.

Enteroviruses have a marked affinity for the muscle, and herpes viruses for nerves.

Its also not ruled out that what I call the multiple hit hypothesis is involved. It could be several different infections or other processes combining to cause ME, and someone might not need to have these happen all at once, they might happen over years or decades.

I still think enteroviruses are the number one potential cause though.
 

Hip

Senior Member
Messages
17,820
@alex3619
So you wouldn't say that some infectious agents can be considered known causes of ME/CFS?

Take a look at these studies and some text excerpts from them:

Chronic fatigue syndrome and arthralgia following parvovirus B19 infection

"CFS may follow acute parvovirus B19 infection; however, attribution of a case of CFS to B19 infection may be extremely difficult in the absence of serological confirmation of acute infection at fatigue onset."


Chronic fatigue syndrome 5 years after giardiasis: differential diagnoses, characteristics and natural course

"The study shows that Giardia duodenalis may induce CFS persisting as long as five years after the infection."


Of course there must be other causal factors involved, because not everyone with the above infections gets ME/CFS. The same is true of poliovirus and poliomyelitis: less than 1% of poliovirus infectees develop paralytic poliomyelitis, so there must be other factors involved in poliomyelitis in addition to poliovirus. But we still say that poliovirus is the cause of poliomyelitis.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
It comes down to mechanisms. Is the pathogen the cause, or is the pathogen something that triggers an autoimmune or autoinflammatory or some other process? So far we do not know for sure, but if I had to bet I would still bet on the pathogens. Even within that a pathogen might use molecular mimicry to cause an immune response.

These days you hear of post-Q fever, post-SARS and I bet in time we might hear of post-guiardia and post-Lyme (which I am starting to read in places). If they can find something they can call a cause they avoid using the terms ME or CFS. I wonder if this is not how they cover up outbreaks, even if not intentionally? I also wonder if the eradication of polio makes ME more prevalent, perhaps not be causing increasing incidence, but by the vaccine doing damage, or the loss of polio means that doctors no longer have a convenient alternative diagnosis to hand.

Too many possibilities ... that's why we can't say anything definitively. That is also why we need exhaustive research into ever single one till we find the cause or causes.
 

Hip

Senior Member
Messages
17,820
If they can find something they can call a cause they avoid using the terms ME or CFS. I wonder if this is not how they cover up outbreaks, even if not intentionally?

This is exactly why I think we should be calling these fatiguing illnesses caused by parvovirus B19, Chlamydia pneumoniae, Coxiella burnetii and Giardia lamblia as proper chronic fatigue syndrome — for both scientific and political reasons.

The symptoms found in the fatiguing illnesses caused by these four pathogens are indistinguishable from the regular idiopathic ME/CFS that most of us have. So logically they should be called ME/CFS, and these four pathogens should be called known causes of ME/CFS.

I make a deliberate point of calling these four pathogens "known causes of ME/CFS" for both scientific and political reasons. And in this study, Dr Chia does likewise, and calls Chlamydia pneumoniae a "treatable cause of CFS".

Why should we not call the diseases caused by these four pathogens as ME/CFS? Not to call them ME/CFS is to play into the hands of the Wessely School psychosomatic classification of ME/CFS. The Wessely School psychiatrists are so strongly attached to their psychosomatic views, that if a category of ME/CFS comes along that has a known physical cause, like the four known causes above, then they shift the goal posts as say "well, that's not ME/CFS". But you should not be allowed to shift the goal posts in this way.

To my mind, it there is clear proof that ME/CFS can be caused by an infection in these four cases.


You don't necessarily have to know the disease mechanism to ascribe causality.

The reason we can be confident in saying that these four pathogens are proven causes of ME/CFS is because:
(1) The symptoms of ME/CFS are often observed to follow an infection with these four infectious agents.
(2) These infectious agents are easily detectible in the blood of these patients with the ME/CFS symptoms.
(3) All these four infectious agents are treatable, and once treated, not only do their levels in the blood decrease, but also the ME/CFS symptoms disappear also.

Put all together, the above observations are proof enough that these four agents cause ME/CFS, even if we do not yet know the mechanism by which they create the ME/CFS symptoms.


Unfortunately in the case of enteroviruses, we do not yet have the same level of evidence. We know from Dr Chia's work, and from the early British researchers, that enterovirus infections are associated with ME/CFS, but of course association does not imply causation.

However, if in the future it can also be shown that:
(1) ME/CFS follows from an acute enterovirus infection, and
(3) Once the enterovirus infection is treated with antivirals, the level of enterovirus in the patient goes down, and the ME/CFS symptoms disappear,

then this will be sufficient evidence to say that enterovirus is also a known cause of ME/CFS.


The above formula for causality relates to Koch's postulates, which are the criteria required to establish a causal relationship between a microbe and a disease.
 
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alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
It comes down to the quality of evidence. We really need some large effective RCTs that can show this. To get those we need interest and funding. It may be doable, but the way things are there is huge resistance to the notion that this range of pathogens cause ME or similar illnesses. Just as there is resistance to the repeated finding of enterovirus in ME patients, or the fact that antivirals to treat herpes viruses get and order of magnitude better result than psychogenic treatment.

I think in Holland patients and even many in the general public regard Q fever as causing ME though.

The other problem is this. Most of these pathogens appear to be hit and run in conventional medical literature. Like with enteroviruses and ME, we have to be able to reliably demonstrate the pathogens are persistent, and not just the syndrome that follows the pathogen attack. That's a long slow scientific process, muddled by the issue that the patient cohorts are often heterogeneous.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Something I have started thinking about again, after putting it on the backburner for several years, is what if the viral model is even more wrong than we know? Viruses are unlike any other lifeform, although there is debate over whether or not they should be considered alive. They have been with us for probably almost as long as there has been life on this planet. Viruses get an advantage from not killing hosts. New viral strains and viruses that cross into other species tend to be more virulent, or at least this has been remarked.

Viruses in acute phase can undergo rapid explosive replication. They evolve fast. That is one reason we have trouble fighting them, both with the body and using science based interventions.

So are we talking enteroviruses or herpes viruses, endogenous HERVs or genetic defects, Lyme or Candida?

What if this is the wrong question?

These pathogens have evolved in the human population for millions of years, though of course not all of them are that old. As the human population increased, and some of these viruses became nearly ubiquitous in adults, the option for co-evolution would have been pervasive and massive. These pathogens have co-evolved. This would come under the heading of evolutionary virology, though not all the pathogens in this would be viruses. Evolutionary pathogenesis perhaps?

So the cause may not be found in one factor, but in how many factors have evolved to combine in non-lethal ways to create ideal hosts.

I have more to say but I only just woke up and I am exhausting fast. Done too much with the IOM thing.
 

Antares in NYC

Senior Member
Messages
582
Location
USA
These two studies show that when the coxsackievirus B (an enterovirus) enters the brain, it infects astroctye cells:

Human astrocytic cells support persistent coxsackievirus B3 infection

Induction of cytopathic effect and cytokines in coxsackievirus B3-infected murine astrocytes

This is clear evidence that this enterovirus can cause a chronic infection in the brain.
Amazing studies. Coxsackievirus B3 rings very close to a potential cause for ME/CFS, in my opinion. It even causes immune disregulation!

@Hip , do you know why there were so many early studies pointing to enteroviruses as the cause of ME/CFS, and then the studies stopped and started pointing in different directions? Is it because of the classification as "chronic fatigue syndrome" in the 1980s? Did any studies disprove the enterovirus theory?
 

Hip

Senior Member
Messages
17,820
do you know why there were so many early studies pointing to enteroviruses as the cause of ME/CFS, and then the studies stopped and started pointing in different directions? Is it because of the classification as "chronic fatigue syndrome" in the 1980s? Did any studies disprove the enterovirus theory?

Yes, I think the erroneous recasting of ME/CFS as a psychogenic disease by the dreadful Wessely School psychiatrists, and the unfortunate fact that these psychiatrists were influential enough to get their views adopted as the official perspective of ME/CFS, probably explains why the enterovirus studies performed by the early British researchers were not followed up — until Dr John Chia picked up the baton, and performed the first studies that replicated the early British enterovirus ME/CFS research.

One of the early proponents of the enterovirus etiology of ME/CFS was the late Dr John Richardson, and in 1999 he published a ME/CFS guidelines paper in which he wrote: "In the UK for 4 - 5 decades, we have found that an initial illness caused by one of the enteroviruses was the most frequent cause of the ensuing illness known as ME."

So it has been known from the 1950s or 1960s that ME/CFS can follow an enterovirus infection.

No studies have disproved the enterovirus theory, though some studies have been unable to find evidence of chronic enterovirus infection in ME/CFS patients, but this is most likely due to the fact that only very low levels of neutralizing antibodies are made in chronic enterovirus infections, so you have to use very sensitive testing if you are going to successfully detect these infections.

What is necessary now is for additional research groups to replicate Dr Chia's work, as this will add even more weight to the enterovirus theory of ME/CFS.
 
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alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
According to Byron Hyde, funding stopped in about 1970 after the McEvedy and Beard paper which claimed ME was mass hysteria. Wessely was late to this bandwagon, but has been busy ever since he started, despite primises he no longer does CFS research.

I think what explains it has nothing to do with Wessely, except that psychogenic proponents have capitalized on it to push their own views. In traditional medical training they are taught the lytic lifecycle for viruses, and probably not much more. They are also taught that we get over a viral infection, and at that point and for considerable time after that we have antibodies.

They are not aware of both failure to seroconvert, and loss of seroconversion, both of which are reported in ME. These will cause either no antibodies or no antibodies after a while.

The are not taught about non-lytic lifecycles of viruses. The research on this is still in its infancy.

They are taught that if tests are negative the pathogen is not present, move on. If antibody titres are very low, then the pathogen is no longer present, then move on.

Non-lytic lifecycles in which there can be a huge viral prevalence in tissues with nothing in the blood and low or no viral titres never occurs to most doctors. This applies to at least herpes and enterviruses. They are aware that herpes viruses are "dormant", which they presume means inactive until they reactivate, as in cold sores or shingles.

It does not occur to them that under alternate viral lifecycles a "dormant" virus can be metabolically active and spreading through the body.

So they test for a virus. Sorry, no virus. Or they test for antibodies, which is cheaper and so probably a preferred test. Sorry, no antibodies. So they reason the virus is not present. If the virus is not present it cannot cause ME and CFS.

This is such a flawed unscientific view that it is astonishing. It also seems to be what most doctors think in my opinion. Doctors are usually NOT medical scientists, and their views are often severely out of touch with the science.

This was probably such a pervasive finding, of no enteroviruses in ME patients, though some old infections in antibodies, that I think it entered medical folklore.

While Wessely and others capitalize on this unscientific view, they are not to blame for it, though they are responsible for the claims they make about it.