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Regular Enteroviruses and Non-Cytopathic Enteroviruses

ttt

Senior Member
Messages
101
Location
Santa Monica, CA
The distinction being made in this thread is between regular enteroviruses, and the noncytopathic enteroviruses. These are two different forms of the same virus.

Thanx, Hip. You know, I actually did know that, which is why I qualified my question as an ignorant one -- I think y'all are a step or two (or three) ahead of me in looking at the difference between a regular enterovirus and a noncytopathic one. I'm still on Step 1 -- the difference between an enterovirus and a regular virus. I Googled it before I asked and couldn't find an answer. I was gonna post a separate thread to ask, but then I saw this thread, and I figured if anyone knows, you guys would know. So I'm hoping someone can explain that difference to me. Thanx! :)
 

voner

Senior Member
Messages
592
.........the virus you are looking for (they are only semi-specific) and if anything is wrong with antibody production, which appears to be the case at least some of the time in ME, then antibody numbers might be lower than they should be, or even nonexistent. Many of us lose the ability to produce antibodies to prior infections - something is wrong with the B cells. We are still trying to figure this out.

alex3169,

have you discussed this with Prof. Edwards on this thread?

http://forums.phoenixrising.me/inde...tatement-on-uk-rituximab-trial-30-july.24499/

I searched about halfway back on it not find anything. Just curious.
 

Hip

Senior Member
Messages
17,824
Here's another I'm just starting on enterovirus and the heart. They successfully used interferon B without relapse and it cleared the virus in the heart. Dr Chia used alpha and delta I believe. Hepatitis is treated with alpha.
http://www.enterovirusfoundation.org/pdfs/research/circulation-article.pdf

That is very interesting. I wonder how ME/CFS patients might response to interferon beta treatment.

As far as I know, interferon beta has not been tried on ME/CFS patients. I understand that Dr Jonathan Kerr wanted to perform such a trial, but funds were not forthcoming. Dr Chia used interferon alpha, gamma and delta in his ME/CFS research, but not beta.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Hi ttt , there are many type of viruses. Enteroviruses are a group of viruses that are part of a larger group called picorna viruses. These are just labels for groups of viruses. Picorna viruses cause many cases of the common cold. Polio virus was an enterovirus. Many potential ME epidemics were closely associated with polio virus. Indeed I wonder if eradication of polio in the Western world has led to a decrease in epidemics, or the relabeling of epidemics is to blame. We don't get ME any more, we get post-Q fever, or post-SARS etc.

So enteroviruses are just viruses that like to infect the gut, but also typically infect the respiratory tract, which is why they can occur with flu-like symptoms. Most importantly this group of viruses can attack B cells, and enteroviruses like living in muscle.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
alex3169,

have you discussed this with Prof. Edwards on this thread?

http://forums.phoenixrising.me/inde...tatement-on-uk-rituximab-trial-30-july.24499/

I searched about halfway back on it not find anything. Just curious.

Hi voner , no I haven't discussed this. One problem is a lot of this is anecdotal - I don't know that a formal study has resulted in showing a loss of seroconversion, but I talk to people in which this happens. Edwards is aware of Bansal's findings, and so of the importance of changes in B cells. The WPI were the first to notice this, but I don't think they published it in a formal paper, they were having more than a few problems at the time. There is also the question of whether this is a general finding, or only right for subgroups. Alex.
 

Hip

Senior Member
Messages
17,824
Thanx, Hip. .... I'm still on Step 1 -- the difference between an enterovirus and a regular virus. I Googled it before I asked and couldn't find an answer. I was gonna post a separate thread to ask, but then I saw this thread, and I figured if anyone knows, you guys would know. So I'm hoping someone can explain that difference to me. Thanx! :)

Enterovirus is just one among many viruses. There are many viruses out there. For example: herpes simplex virus (causes cold sores), human herpes six virus (HHV-6), norovirus (winter vomiting bug), Epstein-Barr virus (the mono virus), varicella zoster virus (causes chicken pox), influenza virus (causes flu), cytomegalovirus, adenovirus, measles virus, West Nile virus, coronavirus, etc, etc.

In other words, an enterovirus is not a special type of virus; it is just the name of a particular virus.

From the ME/CFS perspective, enterovirus is important since there is good evidence linking this virus to ME/CFS, and Dr Chia believes that enterovirus will turn out to be the main cause of ME/CFS. But other viruses have also been linked to ME/CFS — viruses such as Epstein-Barr virus, and HHV-6.

However, Dr Chia's main focus is on enterovirus as the cause of ME/CFS.

Dr Chia often uses the antiviral oxymatrine to treat enterovirus infections in ME/CFS patients.

Incidentally, this info about noncytopathic enteroviruses is quite advanced stuff, so if you are just beginning to learn about these things (as we all were at one stage), I would not be too concerned about this more complex noncytopathic aspect of the enterovirus life cycle.

In terms of the ME/CFS learning curve: a while ago I wrote an introductory article for beginners about the viruses and other microbes that are linked to ME/CFS, and how to test and treat them. That introductory article for beginners is here, in case it is of any use to you:

Chronic Fatigue Syndrome — A Roadmap For Testing And Treatment

 

globalpilot

Senior Member
Messages
626
Location
Ontario
These viruses were cleared by the interferon as shown by PCR of heart biopsy (presumably heart, on a brief read I did not see specific tissue mentioned). There is no guarantee they were completely cleared though, but its a start. Remission would be a better term. These are good results.

One thing that concerns me though is the very high level of infection in patients with ME: way too many cells are infected. As a result if we cause those cells to die it might have very nasty consequences. So far as I am aware this highly pervasive infection by interoviruses is unique to CFS (not using ME criteria here) but I don't know that this has been confirmed.

I have the same concern, which I believe you brought up when DRACO was being discussed. The tissue was heart tissue in this case - the patients have myocarditis. That tissue is non -dividing so they would have the same issue of a lot of cells dying without being replaced. I didn't see that being mentioned.

There is a much larger study that i'll try to get today at the library - also with impressive results.
This could be an important treatment for some of us and I'd like Dr Chias thoughts on it. Is anyone reading this a patient of his ?
 

Hip

Senior Member
Messages
17,824
... if we developed tests for specific viral proteins they might be detectable even in noncytopathic infections, and also that we might have antibodies to those proteins

Dr John Chia, in his study on enteroviral infections in ME/CFS patients (see: Chronic Fatigue Syndrome is Associated With Chronic Enterovirus Infection of the Stomach, John K S Chia, Andrew Y Chia, 2007), was able to detect both normal (lytic cycle) enteroviruses and noncytopathic enteroviruses in ME/CFS patients.

The test Chia used for normal enteroviruses was the immunoperoxidase stain, which detects the enterovirus VP1 protein. The VP1 protein is found in the capsid (the outer shell) of enteroviruses.

I understand that noncytopathic enterovirus RNA was detected in this study by means of a "Qiagen one-step RT-PCR enzyme kit".

In the study, normal (lytic cycle) enteroviruses were not always found in ME/CFS patients, even when enteroviral RNA had been detected. This finding suggests that noncytopathic enteroviruses, rather than regular (lytic cycle) enteroviruses, may be playing the major role in ME/CFS.
 

Hip

Senior Member
Messages
17,824
Does an Allergen in the Enterovirus VP1 Protein Cause ME/CFS?

One important unanswered question in enterovirus-associated ME/CFS is: how does the very low level of enterovirus infection found in ME/CFS patients apparently cause the metabolic chaos that is chronic fatigue syndrome?

That is to say, how does a feeble chronic enterovirus infection, slowly smoldering away in the body, which creates so few viral particles, and is barely detectable by antibody testing, seemingly cause so much trouble and havoc — a degree of havoc way beyond what the few enteroviral particles found in the tissues should be able to create? How does such a low level infection cause a condition as severe as ME/CFS?


Noncytopathic enteroviruses are one answer to this question:

The idea that noncytopathic enteroviruses, hidden within human cells and not detectable by antibody testing, may be the root of all the trouble in ME/CFS is one possible answer to this question. Normal antibody testing does not detect noncytopathic enteroviruses, only regular enteroviruses, and Dr Chia has shown that ME/CFS patients can have very low levels of regular enteroviruses in their body, yet have a substantial noncytopathic enterovirus infection.


Another possible (though very speculative) answer to this question I'd like to offer relates to an enterovirus–allergen connection I read about in a blog article by Dr Art Ayers:

Dr Ayers said that the enterovirus VP1 protein contains an allergen. (The VP1 protein forms part of the out shell of enteroviruses). Specifically, Ayers states he has detected an amino acid sequence in the VP1 protein of enteroviruses that he also found in all allergens — allergens such as peanut, ragweed, dust mite, bee venom — as well as in the autoantigens of autoimmune diseases like lupus and multiple sclerosis. Ayer's article is HERE.

So I was wondering whether such an allergen in the enterovirus VP1 protein might, even at the low level of enteroviral particles present in ME/CFS patients, be precipitating an allergic and/or autoimmune condition in the body which could underpin ME/CFS. You only need a tiny amount of allergen to provoke a large pathological response in the body, so this might explain how the low levels of enteroviral particles found in ME/CFS patients can precipitate such a significant pathological response.

I wrote a thread HERE about the observation that enterovirus VP1 protein contains an allergen.
 

Sparrowhawk

Senior Member
Messages
514
Location
West Coast USA
Damn Hip, that is one zinger of a theory. For them of us who have always had allergies and high inflammatory response to the outside world, not a bad hypothesis.

Layman leap in logic here, but might things like vaccinations trigger or exacerbate this? I am just looking for a link to those who say their illness was precipitated by a vaccination. Add other system irritants such as stress, food intolerances, pollution, mold exposure, whatever to the mix and it could be that we have an additive situation, where allergy to foriegn but internal proteins is the perpetuating factor that keeps the body immune response so tilted and tired.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
On possible VP1 and allergens, it depends on the 3D folding of the protein. An amino acid sequence is not enough, its the 3D structure including electric charges that create the target for antibodies. Its about the exact shape and charge of the amino acids on the outside of the protein. However there is one condition under which all allergens are the same in this respect: proteins that lose their 3D structure are called denatured. They become long strings of amino acids, not folded up into a ball. If conditions exist for that to happen, and we develop antibodies to similar proteins, then they would cross react.

I have dust mite allergy, and coxsackie B3 virus by antibody assay, though that test was done 24 years ago now.

Once we start targeting the protein though, we could develop autoantibodies to other parts of the sequence. These might cross react with many endogenous proteins.
 

Hip

Senior Member
Messages
17,824
Sparrowhawk The vaccination that seems to precipitate ME/CFS more than other vaccinations is the hepatitis B vaccination.

I do tend to think that ME/CFS generally arises from a combination of causal factors, rather than just one factor. In my opinion, the co-factors I think are most likely playing a causal role in precipitating ME/CFS are:

• Already having irritable bowel syndrome (refs: 1 2 3) or small intestine bacterial overgrowth (refs: 1 2).
• Already having interstitial cystitis or overactive bladder. (refs: 1 2 3 4).
• Significant exposure to mold toxins (refs 1 2).

All of the above have been shown to occur more frequently in ME/CFS patients (refs given). I myself had IBS and overactive bladder prior to catching the enterovirus infection that seemed to trigger my ME/CFS. I suspect my ME/CFS arose due to the combined effects of all these three factors, though my hunch is that my enterovirus infection played the major casual role (this is because I had both IBS and overactive bladder for many years with developing ME/CFS; but soon after catching an enterovirus, I began to descend into ME/CFS).

Other observed (but very rare) triggers of ME/CFS include: physical trauma (particularly a motor vehicle accident), major surgery, meningitis, and certain focal infections, particaulry jaw bone infections. Hepatitis B vaccination would fit into this list of very rare triggers.

Silicone (when used for breast and other implants, as well as in silicone injections) can very rarely cause a ME/CFS-like illness, as can exposure to significant amounts of organophosphate or pyrethroid pesticides.
 
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Hip

Senior Member
Messages
17,824
A video of a presentation given by Dr John Chia, detailing his work with oxymatrine and intravenous interferon treatments for ME/CFS, and his research into the double stranded RNA enterovirus infection (aka: the non-cytopathic enterovirus infection) he thinks is a primary cause of ME/CFS, is to be found >> HERE.
 
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jepps

Senior Member
Messages
519
Location
Austria
Sparrowhawk
I do tend to think that ME/CFS generally arises from a combination of causal factors, rather than just one factor. In my opinion, the co-factors I think are most likely playing a causal role in precipitating ME/CFS are:

• Already having irritable bowel syndrome (refs: 1 2 3) or small intestine bacterial overgrowth (refs: 1 2).
• Already having interstitial cystitis or overactive bladder. (refs: 1 2 3 4).
• Significant exposure to mold toxins (refs 1 2).

I suspect my ME/CFS arose due to the combined effects of all these three factors, though my hunch is that my enterovirus infection played the major casual role (this is because I had both IBS and overactive bladder for many years with developing ME/CFS; but soon after catching an enterovirus, I began to descend into ME/CFS).

.

Very interesting, what you write, Hip. I´m treating fungi since , and do bioenergetic testing, I can read the diagnosis of the actual processes a monitor. Many do not trust this diagnosis, but very often, when I read a diagnosis, then I search for a research, and I´m finding a correlation, what the diagnosis shows. The last test showed the excretion of mercury, and enterovirus, I have symptoms of mild myocarditis, and I found this:

http://www.ncbi.nlm.nih.gov/pubmed/18357775

http://www.ncbi.nlm.nih.gov/pubmed/21984480

Low-dose inorganic mercury increases severity and frequency of chronic coxsackievirus-induced autoimmune myocarditis in mice.
Nyland JF1, Fairweather D, Shirley DL, Davis SE, Rose NR, Silbergeld EK.
Author information

Abstract
Mercury is a widespread environmental contaminant with neurotoxic impacts that have been observed over a range of exposures. In addition, there is increasing evidence that inorganic mercury (iHg) and organic mercury (including methyl mercury) have a range of immunotoxic effects, including immune suppression and induction of autoimmunity. In this study, we investigated the effect of iHg on a model of autoimmune heart disease in mice induced by infection with coxsackievirus B3 (CVB3). We examined the role of timing of iHg exposure on disease; in some experiments, mice were pretreated with iHg (200 μg/kg, every other day for 15 days) before disease induction with virus inoculation, and in others, they were treated with iHg after the acute (viral) phase of disease but before the development of dilated cardiomyopathy (DCM). iHg alone had no effect on heart pathology. Pretreatment with iHg before CVB3 infection significantly increased the severity of chronic myocarditis and DCM compared with control animals receiving vehicle alone. In contrast, treatment with iHg after acute myocarditis did not affect the severity of chronic disease. The increased chronic myocarditis, fibrosis, and DCM induced by iHg pretreatment were not due to increased viral replication in the heart, which was unaltered by iHg treatment. iHg pretreatment induced a macrophage infiltrate and mixed cytokine response in the heart during acute myocarditis, including significantly increased interleukin (IL)-12, IL-17, interferon-γ, and tumor necrosis factor-α levels. IL-17 levels were also significantly increased in the spleen during chronic disease. Thus, we show for the first time that low-dose Hg exposure increases chronic myocarditis and DCM in a murine model.

PMID

This means, that the myocarditis persists, when the patient had exposition to mercury. Mercury alone did not cause myocarditis, coxsackie alone caused a mild myocarditis. The earlier mercury exposition caused chronic myocarditis.

With treating candida mercury of amalgame is released, I assume, the releasing mercury was the reason why coxsackie comes up. There might be a correlation of compromised gut and fungi/heavy metals/viruses, and all causes must be addressed.
 
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Hip

Senior Member
Messages
17,824
This means, that the myocarditis persists, when the patient had exposition to mercury.

Are you sure you quoted the correct study? Nothing in the study you quoted indicates coxsackievirus B (CVB) myocarditis persists when mercury is present.


However, this murine study does focus on mercury in CVB autoimmune myocarditis. Myocarditis is the inflammation of the heart muscle caused by infection or immune problems. Researchers such as Prof Nora Chapman think that chronic myocarditis may make a good model for studying the chronic CVB infections found in many ME/CFS patients.

The study I cited found that inorganic mercury exposure before the initial acute CVB infection increases the severity of the subsequent chronic CVB autoimmune myocarditis. However, the study also found that inorganic mercury exposure occurring after the acute CVB infection did NOT worsen the chronic autoimmune myocarditis.

In other words, the level of mercury in your body at the time you caught the CVB infection has an effect on how severe the subsequent chronic CVB autoimmune myocarditis gets; but any further exposure to inorganic mercury in the chronic stage of infection does not worsen the myocarditis.

So this perhaps suggests that for ME/CFS patients with a chronic CVB infection, any further exposure to inorganic mercury (such as from dental amalgams) will not make the CVB infection worse, at least in regards its autoimmune aspects. And it perhaps also hints that trying to remove mercury from your body will have no benefit in terms of ameliorating the CVB infection.
 
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jepps

Senior Member
Messages
519
Location
Austria
Are you sure you quoted the correct study? Nothing in the study you quoted indicates coxsackievirus B (CVB) myocarditis persists when mercury is present.

Upps:bang-head::bang-head::bang-head::bang-head:

Thank you, Hip, I edited my post, and posted the correct research. It´s the same you found.

As coxsackie is very common in chronic inflammation, and remissions occur, why should not the myocarditis heal, when mercury is detoxed and coxsackie is treated?
I find it interesting, because I do not specific treatment for coxsackie, but only for the gut and fungi. Treating fungi means releasing heavy metals because of its relationship to fungi. And when mercury is released, infections are coming up.
 

Hip

Senior Member
Messages
17,824
As coxsackie is very common in chronic inflammation, and remissions occur, why should not the myocarditis heal, when mercury is detoxed and coxsackie is treated?

I suspect it may be because autoimmunity once triggered is very hard to stop. This means that even if you later remove the factors such as mercury that first helped trigger the autoimmune condition, the autoimmunity will not go away.

Perhaps @Jonathan Edwards may want to comment.


Though I should point out that I have seen no evidence that mercury plays a role in ME/CFS etiology, nor any evidence that mercury detoxification improves ME/CFS.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
I suspect it may be because autoimmunity once triggered is very hard to stop. This means that even if you later remove the factors such as mercury that first helped trigger the autoimmune condition, the autoimmunity will not go away.

Perhaps @Jonathan Edwards may want to comment.


Though I should point out that I have seen no evidence that mercury plays a role in ME/CFS etiology, nor any evidence that mercury detoxification improves ME/CFS.

This all looks a terrible muddle to me. I am not sure where autoimmunity comes in. As far as I know coxsackie virus has nothing to do with autoimmunity in humans and probably not in mice. They talk of a 'model of autoimmunity' but maybe that just means they hope it is a bit like autoimmunity.

As I understand it coxsackie virus can produce a severe myocarditis in humans that can lead to long term heart failure because of muscle damage. I assume that the virus is normally neutralised by the immune system over a period of two to three weeks but it may be that the immune response is an important factor in the damage. That is not autoimmunity though. I cannot see where mercury comes in!
 

Hip

Senior Member
Messages
17,824
As I understand it coxsackie virus can produce a severe myocarditis in humans that can lead to long term heart failure because of muscle damage. I assume that the virus is normally neutralised by the immune system over a period of two to three weeks but it may be that the immune response is an important factor in the damage.
Apparently more recent research (by Profs Steven Tracy and Nora M. Chapman) has shown that in chronic CVB myocarditis, the virus is not entirely neutralized, but rather exists in a different viral form: one that persists on a long term basis as an intracellular infection. This intracellular form of CVB is called a non-cytolytic, non-cytopathic or terminally-deleted (TD) virus.

This terminally-deleted virus is thought may have major import for coxsackievirus B-associated ME/CFS as well.

Here is an extract of an article about this discovery of the TD form of coxsackievirus B in myocarditis:
Interestingly, in those adult cases of myocarditis in which the presence of virus was shown by detecting the viral RNA, rarely can an infectious virus be isolated. This is confusing: how can one detect viral RNA and not detect the virus? And indeed, this was a conundrum for many years.

...

We decided to examine the entire viral RNA genome that was present in these mouse heart samples, asking the basic question: are there deletions anywhere else that might explain this odd phenomenon? When this was done, we discovered that one of the ends of the single strand of RNA that makes up the viral genome, was missing: these viral genomes were then called 'terminally deleted' or TD. What makes this discovery fascinating to virologists, is that the sequence which the virus naturally deletes, was hitherto thought to be absolutely essential for virus replication. Our results, however, showed that while this sequence was very important for efficient CVB replication, it could nonetheless be done away with, and yet have the virus survive.

The cost of this survival is, however, extremely slow replication. A further cost is that this survival can occur only in cell populations that do not divide anymore or divide very infrequently as in muscle tissue. It is this reason why we were able to find these novel virus populations in heart muscle of experimentally inoculated mice and later, in human heart.
...

These results provided an answer to the conundrum of failing to find cytopathic virus in myocarditic heart samples despite the ability to find viral RNA. Indeed, virus (in TD form) does exist in such samples but because the TD populations replicate so slowly and produce so little virus, they are difficult to detect. However, because the defect is not in a part of the viral genome that makes viral proteins, they do make all the viral proteins and even virus particles. But what does the finding of TD genomes mean for HEV disease?

Source: Human Enteroviruses and Chronic Infectious Disease, Steven Tracy and Nora M. Chapman.


That is not autoimmunity though. I cannot see where mercury comes in!
So you are saying that although this murine model of myocarditis involves heart muscle damage arising out of the immune response (and damage which was exacerbated by mercury pretreatment), this immune response cannot really be classified as an autoimmune one.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
So you are saying that although this murine model of myocarditis involves heart muscle damage arising out of the immune response (and damage which was exacerbated by mercury pretreatment), this immune response cannot really be classified as an autoimmune one.

Yes, autoimmunity is something quite different - an immune response involving specific B (or perhaps T) cell reactivity to a self antigen. The problem is that the two situations have been confused ever since it was suggested that in rheumatic fever there was 'cross-reactivity' with self.