Enterovirus in Chronic Disease (NOT just Coxsackie B & Echo)

sometexan84

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Wanted to create a new thread, based on what @Hip said here.

If you suspect Coxsackie A, Enterovirus D-68, or another EV that isn't Coxsackie B or Echovirus, please share in a response!

We often talk about Coxsackie B and Echovirus in ME/CFS, and not the dozens of others types of Enterovirus, many of which could be involved in chronic illness and even ME/CFS.

Much of this discussion stems from Dr. John Chia's research where he's found active Enterovirus in ME/CFS patients, and treated them w/ Interferon (amongst other things).

When Chia mentions specific Enteroviruses in his studies, it's always CVB 1-6, or Echo 11 (sometimes Echo 6, 7, 9, or 30).

Thing is, Dr Chia is as limited as we are, having to rely on the (2) ARUP lab tests, which only account for 11 types of Enterovirus. But in reality, there's SO many more Enteroviruses.

So the question is, do Enteroviruses... other than these 11... cause chronic illness... and could they be involved in ME/CFS?

TWO IMPORTANT PARTS HERE - Part I includes articles/links to studies. Part II is proof from an actual PR member.

Below are some articles that perhaps suggest other Enteroviruses do/can in fact cause chronic illness. Sadly, we cannot test for these.

Part I

Higher abundance of enterovirus A species in the gut of children with islet autoimmunity
https://www.nature.com/articles/s41598-018-38368-8

Here, Enterovirus B was found frequently.. though, the most frequent was actually Coxsackie A2, A4, and A16, in those w/ Type 1 Diabetes

Comparison of Neutralizing Antibody Response Kinetics in Patients with Hand, Foot, and Mouth Disease Caused by Coxsackievirus A16 or Enterovirus A71: A Longitudinal Cohort Study of Chinese Children, 2017–2019
https://www.jimmunol.org/content/early/2022/06/30/jimmunol.2200143

This article shows CVA16 and EVA71, in Hand Foot and Mouth Disease... persisting for >26 months. Though the EV-A71 seems to have a larger negative effect on patients.

Enterovirus and Encephalitis
https://www.frontiersin.org/articles/10.3389/fmicb.2020.00261/full

This shows how EV-A71 can persist, and w/out using cytopathic pathways, but instead can spread non-lytically (just like Coxsackie B and Echovirus in ME/CFS).

Exploring a prolonged enterovirus C104 infection in a severely ill patient using nanopore sequencing
https://academic.oup.com/ve/article/8/1/veab109/6550567

This shows a patient w/ a persistent EV C104. C104 was only discovered in 2005... Interferon Lambda had only been discovered 1 yr prior

CDC Warns About Rhinovirus and Enterovirus-D68: What to Know
https://www.healthline.com/health-n...e-disease-experts-think-will-return-this-fall

EV D68 is another "newish" one. But you see it now mostly associated w/ Acute Flaccid Myelitis.

The quote below.... what does this remind you of......

“Unfortunately, there are no collective data or any systemic reviews, but most of the patients seem to end up with some persistent and residual symptoms,” Al-Habib said.

Part II

He's shared this before here on PR. But this is direct proof that other Enteroviruses can cause ME/CFS.

@EddieB went to Dr. Chia and had his Enterovirus staining done from stomach biopsy. It showed massive Enteroviral presence. Eddie's been sick w/ ME/CFS LONG time.

ALSO, he has in fact had both ARUP lab tests done and was negative for ALL 11 viruses, including the 6 Coxsackie B and 5 Echovirus.

This means he has another type of Enterovirus in his gut causing his illness.
 
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Hip

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Higher abundance of enterovirus A species in the gut of children with islet autoimmunity
https://www.nature.com/articles/s41598-018-38368-8
Out of the studies you listed above, this is the only one which comes near to linking enterovirus A to a chronic disease. Islet autoimmunity is not a disease itself, but is a precursor to type 1 diabetes.

But this paper does not just link CVA to islet autoimmunity, but dozens of non-enteroviruses too (if you look at figure 3, the blue and red dots are enterovirus, but they are outnumbered by the grey dots, which are non-enterovirus).

So this paper is not really specific for enterovirus A, in spite of its title.


Type 1 diabetes has however been linked to a coxsackievirus B4 infection of the islet cells themselves, and this infection is thought to be one of the factors which destroys these cells in T1D.



He's shared this before here on PR. But this is direct proof that other Enteroviruses can cause ME/CFS.

@EddieB went to Dr. Chia and had his Enterovirus staining done from stomach biopsy. It showed massive Enteroviral presence. Eddie's been sick w/ ME/CFS LONG time.

ALSO, he has in fact had both ARUP lab tests done and was negative for ALL 11 viruses, including the 6 Coxsackie B and 5 Echovirus.

This means he has another type of Enterovirus in his gut causing his illness.
There are 32 human echovirus. ARUP lab only tests for 5 out of these 32 (it tests for echovirus 6, 7, 9, 11 and 30). So EddieB could well have one of these other non-tested for echoviruses driving his ME/CFS.

So his story is not proof that an enterovirus outside of the CVB and echovirus groups can cause ME/CFS.
 

sometexan84

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@Hip I also would like to quote you. You said this elsewhere, not in this forum, but you did say this...

Interesting about enterovirus D68. I found a Dr Chia paper which suggests enterovirus D68 can form chronic infections: https://www.scirp.org/journal/paperinformation.aspx?paperid=68604

Our laboratory demonstrated persistent, non-cytopathic EV D68 infection in Hela cells beyond 2 months (author’s unpublished observation).
So this is a non-cytolytic D68 infection that was active for over 2 months.
 

sometexan84

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There are 32 human echovirus. ARUP lab only tests for 5 out of these 32 (it tests for echovirus 6, 7, 9, 11 and 30). So EddieB could well have one of these other non-tested for echoviruses driving his ME/CFS.

So his story is not proof that an enterovirus outside of the CVB and echovirus groups can cause ME/CFS.
But really I was trying to show that we can have an Enterovirus which ARUP can't detect, nor can any lab. So, not just like CVA, or EVD, etc.. but also other Coxsackie B's and Echoviruses.

I know that goes against the title of this thread. But I couldn't make the title super long to cover all the specifics.
 

Hip

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@Hip I also would like to quote you. You said this elsewhere, not in this forum, but you did say this...

Interesting about enterovirus D68. I found a Dr Chia paper which suggests enterovirus D68 can form chronic infections: https://www.scirp.org/journal/paperinformation.aspx?paperid=68604

Our laboratory demonstrated persistent, non-cytopathic EV D68 infection in Hela cells beyond 2 months (author’s unpublished observation).

So this is a non-cytolytic D68 infection that was active for over 2 months.
That's true. Although a persistent infection in a cell line does not necessarily mean that the virus can cause a chronic disease.

Our bodies are full of persistent viruses (many with obscure names that people will not have heard of), but these viruses may be benign in many cases, and not be linked to any disease.


One apparent persistent enterovirus infection outside of enterovirus B which is linked to chronic disease is the poliovirus infection that has been found in some post-polio syndrome patients. Post polio is an illness that may hit people who had polio in their youth. It seems like the poliovirus can live in the brain for decades without causing issues, and then suddenly trigger post-polio syndrome (although the jury is still out as to whether the poliovirus causes post-polio syndrome).

Poliovirus is from the enterovirus C species (this species also contains some CVAs).
 
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sometexan84

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That's true. Although a persistent infection in a cell line does not necessarily mean that the virus can cause a chronic disease.

Our bodies are full of persistent viruses (many with obscure names that people will not have heard of), but these viruses may be benign in many cases, and not be linked to any disease.
I'll make a bold claim here.

Theory Only, and solely my opinion: If you have a persistently active infection, you will likely get persistent (chronic) symptoms... as long as it's active. They may be more severe in different cases, but there is a problem and there will be consequences.

Can you tell me some persistent viral infections that aren't in the Herpesviridae family? If anyone can tell me of a viral infection that can be active persistently and cause no symptoms, do share. I don't think this exists. But am certainly open to learning.
 
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I'll make a bold claim here.

Theory Only, and solely my opinion: If you have a persistently active infection, you will likely get persistent (chronic) symptoms... as long as it's active. They may be more severe in different cases, but there is a problem and there will be consequences.

Can you tell me some persistent viral infections that aren't in the Herpesviridae family? If anyone can tell me of a viral infection that can be active persistently and cause no symptoms, do share. I don't think this exists. But am certainly open to learning.

Also apparently 10-30% of population has IBS.

Chias healthy controls in stomach biopsy.... Exactly 20% had VP1 protein stain. So, that's literally dead center of the estimated IBS sufferers group.
 

Hip

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If anyone can tell me of a viral infection that can be active persistently and cause no symptoms, do share.
Enterovirus itself is an example. Remember all the early British research on enterovirus ME/CFS, where in the late 1980s and 90s researchers performed muscle biopsies on ME/CFS patients, and tested the muscle tissue for enterovirus using PCR (PCR had only just been developed at that time).

They found enterovirus RNA in the muscles of ME/CFS patients much more commonly than in healthy controls. But enterovirus was also present in a small percentage of healthy controls.

At the time, this presence of enterovirus in the muscles of healthy people put the dampers on the enterovirus theory of ME/CFS, because clearly the presence of enterovirus in the muscles was not 100% correlated to who had ME/CFS and who was healthy.



But the world of human viruses is much larger than just the enteroviruses and herpesviruses that we focus on in ME/CFS.

One virus I took an interest in some years ago is Saffold virus, which is from the Cardiovirus genus, which in turn is within the Picornavirus family (enterovirus of course is also in this Picornavirus family).

Saffold virus was only discovered in 2007, but it was found to be living in humans: this PCR study for example finds Saffold virus living in the adenoids of 15% of humans. And something like 90% of the population have antibodies to Saffold virus, suggesting either past infection in these people, or that the Saffold virus may be present in the tissues or organs as a chronic active low-level infection.

Another newly-discovered viral genus just from the Picornavirus family is the Cosavirus genus, discovered 2008, which has been found by PCR in the faeces of 33.8% of healthy children.



Below is a list of all the viral families which infect humans. In each family, you may have dozens of genera, and within each genus, you may have dozens of individual viral species. So you can see that there are 1000s of viruses which infect humans.

And if you Google any one of these viruses, you will often find that they are present in a substantial percentage of the healthy population.

List of Human Viral Families
  • Adenoviridae
  • Anelloviridae
  • Arenaviridae
  • Astroviridae
  • Bornaviridae
  • Bunyaviridae
  • Caliciviridae
  • Coronaviridae
  • Filoviridae
  • Flaviviridae
  • Hepadnaviridae
  • Hepeviridae
  • Herpesviridae
  • Orthomyxoviridae
  • Papillomaviridae
  • Paramyxoviridae
  • Parvoviridae
  • Picobirnaviridae
  • Picobirna
  • Picornaviridae
  • Pneumoviridae
  • Polyomaviridae
  • Poxviridae
  • Reoviridae
  • Retroviridae
  • Rhabdoviridae
  • Togaviridae
  • Deltae
Source: here
 
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Muscle biopsy study https://jnnp.bmj.com/content/74/10/1382

"Results: Muscle biopsy samples from 20.8% of the CFS patients were positive for enterovirus sequences by RT-NPCR, while all the 29 control samples were negative; 58.3% of the CFS patients had a SATET+ response. Nine of the 10 enterovirus positive cases were among the 28 SATET+ patients (32.1%), compared with only one (5%) of the 20 SATET− patients. PCR products were most closely related to coxsackie B virus."

Not sure if this is the one you meant hip but maybe it is.

Interestingly or maybe not significant upon reflection but those who did the exercise test ended up with the higher concentration of entereovirus from biopsy. Which maybe isn't surprising but I hadn't seen that correlation before in a study.
 

sometexan84

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Enterovirus itself is an example. Remember all the early British research on enterovirus ME/CFS, where in the late 1980s and 90s researchers performed muscle biopsies on ME/CFS patients, and tested the muscle tissue for enterovirus using PCR (PCR had only just been developed at that time).

They found enterovirus RNA in the muscles of ME/CFS patients much more commonly than in healthy controls. But enterovirus was also present in a small percentage of healthy controls.

At the time, this presence of enterovirus in the muscles of healthy people put the dampers on the enterovirus theory of ME/CFS, because clearly the presence of enterovirus in the muscles was not 100% correlated to who had ME/CFS and who was healthy.
You're suggesting Enterovirus is persisting in these healthy controls.

Let's look at the 80's and 90's muscle biopsy ME/CFS studies you're referring to...

These below found Enterovirus is zero controls. So I assume you're not talking about them

1664507584808.png

1664507685634.png

1664507737482.png



This study below is more likely what you're referring to, as it showed 53% ME/CFS and 15% enterovirus RNA in healthy controls.

This section from mepedia should be edited, as these were not "healthy controls". In fact, of the 6 (15%) controls that had the EV RNA, all had a malignant tumor, 5 breast and 1 colon. They may not have had CFS, but they were ill and not w/out symptoms.

1664507975318.png


I'd also like to add that, in the above study, they used PCR with 5' (read as "five prime") for detection. As you are aware, our persistent enterovirus has the 5' end of the viral genome completely deleted.

It's possible that some EV w/ 5' still in tact exists within us... but if it does (and that's a big IF), it's extremely minute.

It's likely that the 5' EV RNA will exist in us for a while, even when we have CFS already. But it mostly all ends up getting chopped off as a survival mechanism of EV.

1664508461340.png


What I'm saying is that, these old studies that use the 5' method of detection are faulty. This is likely better for detecting acute infection, and not the mutated persistent form where 5' no longer exists.


At the time, this presence of enterovirus in the muscles of healthy people put the dampers on the enterovirus theory of ME/CFS, because clearly the presence of enterovirus in the muscles was not 100% correlated to who had ME/CFS and who was healthy.
And this was the whole purpose for this 2021 article. To shed light on these past studies and their shortcomings....

The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253308/

The rest of what you wrote doesn't address what I'd suggested. I'm talking about active and persistent viruses, those that linger and do not appear to go away. And how this causes symptoms.
 
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Hip

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I'd also like to add that, in the above study, they used PCR with 5' (read as "five prime") for detection. As you are aware, our persistent enterovirus has the 5' end of the viral genome completely deleted.
That's something I have wondered about too. Though not all of the 5′ untranslated region is deleted in non-cytolytic enterovirus: the enterovirus 5′UTR is 750 nucleotides in length, whereas the maximum length of the deletions is 49 nucleotides, and some deletions are shorter than 49 nt, according to work by Prof Nora Chapman.

So if the PCR primer targets an region away from the last 49 nucleotides at the end of the 5′ untranslated region, it will still detect enterovirus, even when it turns into non-cytolytic enterovirus.



Another example of a chronic infection causing no disease is HIV: in most people, HIV causes the disease of AIDS (unless they take antiretrovirals). But around 1% of the population are immune to AIDS, and these people can have HIV living in their body without developing AIDS.

HTLV is another example: in the Carribbean, Florida and Japan, HIV's cousin HTLV is rife, with up to 5% of the population having HTLV in their bodies. But only about 1% of these carriers will develop the neurological disease that HTLV causes; the other 99% will carry this retrovirus without succumbing to disease.
 

sometexan84

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That's something I have wondered about too. Though not all of the 5′ untranslated region is deleted in non-cytolytic enterovirus: the enterovirus 5′UTR is 750 nucleotides in length, whereas the maximum length of the deletions is 49 nucleotides, and some deletions are shorter than 49 nt, according to work by Prof Nora Chapman.

So if the PCR primer targets an region away from the last 49 nucleotides at the end of the 5′ untranslated region, it will still detect enterovirus, even when it turns into non-cytolytic enterovirus.
My point is that this was not the best detection method for persistent enterovirus. But they didn't know about the 5' deletions back then.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253308/
"RT-PCR experiments that use primers directed at the 5′UTR of enteroviruses can be problematic if the enterovirus contains mutations within the primer binding region, as is known to happen during persistent infection"

Though you are right that the 5'UTR is not completely deleted, rather it's a 5' terminal deletion of the genome.
 

sometexan84

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Another example of a chronic infection causing no disease is HIV: in most people, HIV causes the disease of AIDS (unless they take antiretrovirals). But around 1% of the population are immune to AIDS, and these people can have HIV living in their body without developing AIDS.
This cannot be true. Do you have references?

If HIV keeps multiplying, you should eventually get symptoms...


HTLV is another example: in the Carribbean, Florida and Japan, HIV's cousin HTLV is rife, with up to 5% of the population having HTLV in their bodies. But only about 1% of these carriers will develop the neurological disease that HTLV causes; the other 99% will carry this retrovirus without succumbing to disease.
HTLV is another one like herpesvirus. It can become latent and can be re-activated. So it's not necessarily an active persistent virus.
 

Hip

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Do you have references?
I have references, and in this post explain how anyone can check to see if they are immune to AIDS, using their 23andme results!



HTLV is another one like herpesvirus. It can become latent and can be re-activated. So it's not necessarily an active persistent virus.
That's true, I think HTLV becomes latent in most people, and in these cases does not cause disease.

Though of course viruses can wake up from latency when the person is feeling run down, and their immunity weakens. For example, herpes simplex which is latent around the mouth can erupt into cold sores when you are under the weather.

Also, in some cases even latent viruses can be active. EBV for example has 3 states of latency, and in some of those states, the virus is actively making viral proteins. If it is making proteins, it can interfere with cellular or bodily functioning just like an active viral infection does.

There was also a theory that a viral protein called SITH-1 that HHV-6 makes while in its latent state might be the cause of depression and chronic fatigue syndrome.
 

Hip

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If you have a persistently active infection, you will likely get persistent (chronic) symptoms... as long as it's active. They may be more severe in different cases, but there is a problem and there will be consequences.
Did you ever see my summary of the ill health effects, clinical and subclinical, that my nasty coxsackievirus B4 virus caused in the 30+ people who caught it from me?

With this nasty CVB4 virus, which tended to cause low-level persistent infections in pretty much everyone who caught it from me, everyone suffered some long-term adverse effects, though these effects were often subclinical (by subclinical I mean a doctor would not diagnose a disease, but nevertheless the physical or mental health of the person became impaired after catching the virus).

So my virus would tend support your hypothesis that any persistent infection has consequences.

Though I think my virus is a more virulent than normal coxsackievirus B, and I suspect more benign enteroviruses might be able to exist as a persistent low-level infection without any significant ill health effects.



The British family GP and enterovirus ME/CFS expert Dr John Richardson however believed that catching CVB always had consequences. He would note that once one member of a family had developed an illness caused by catching CVB, within a short time, other members of the family would come to him with sudden mysterious health problems, which he would put down to the virus spreading in the family.

So Richardson was of the belief that once CVB spread through a family, it would tend to give rises to ailments in many of the family members. This is certainly what I observed with my own CVB4 virus.
 
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