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Enterovirus and treatments

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Messages
263
In Chia's study the Pleconaril did work for 1 out of 4 patients, but she relapsed shortly after treatment. Pleconaril was denied FDA approval and isn't available anymore anyways.

Yes, he did find virus in the plasma and PBMCs as reported in his paper. Check out this table. The interesting part is that he found patients blood samples would fluctuate between positive and negative for enteroviral RNA over time.

I think that's why Chia prefers tissue biopsies, much more reliable.
 

halcyon

Senior Member
Messages
2,482
In my correspondence with EV Med with the VP1 testing I had primarilarly via Lucila Chia, I was informed Pleconaril does not work once the virus "penitrates the cell" - maybe the academics here can define what that means exacterly?
That is accurate. Pleconaril is an uncoating inhibitor, which means it prevents the viral RNA from exiting the capsid once it has latched on to the cell.
 

Hip

Senior Member
Messages
17,824
Note: this intracellular enterovirus infection found inside cells, and comprising a mixture of positive single-stranded RNA, negative single-stranded RNA and double-stranded RNA, goes by number of names, including the: non-cytolytic enterovirus, non-cytopathic enterovirus, terminally-deleted enterovirus, and defective enterovirus.

Dr Chia has explained in his video presentations that this process of two strings of single stranded RNA combining together to form one string of double-stranded RNA is actually a reversible process: as I understand, it is thought that the double-stranded RNA can also split apart again, and revert back to two strings of single stranded RNA again.

Dr Chia describes this enterovirus double-stranded RNA as the the "seeds" of this non-cytolytic intracellular infection. Seeds are very hardy, and you can destroy a plant, but it can regrow again from its hardy seeds. Likewise, the double-stranded RNA is very hardy, and may be involved in the spread of these non-cytolytic infections from cell to cell.


In terms of manufacturing viral proteins inside the cell, I believe only the positive single-stranded RNA can be used to do this. The double-stranded RNA is hardy, but I don't think this can used to express and manufacture viral proteins.

There is a thread here about how non-cytolytic enteroviruses infections may spread from cell to cell.



In coxsackievirus B myocarditis, you can detect enteroviral RNA, but you often fail to detect any viral particles. Initially researchers found this very mysterious, because if you can find viral RNA, you would expect to find viral particles, because these two normally come together.

But once non-cytolytic enteroviruses were discovered, they explained these findings: the enteroviral RNA found even in the absence of any viral particles actually likely comes from the non-cytolytic virus.


A slide from Dr Chia detailing the non-cytolytic virus (single and double stranded RNA):
Dr Chia Presentation- non-cytolytic virus.jpg



Note that enteroviruses are not the only type of virus that develop into non-cytolytic infections. Google search on the terms: non-cytolytic virus, non-cytopathic virus, defective virus and terminally-deleted virus for more info on non-cytolytic viral infections in general.

More info:
Non-cytolytic / non-cytopathic / defective enterovirus — MEpedia
 
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knackers323

Senior Member
Messages
1,625
Great info Hip. Are some peoples immune systems able to kill off or keep under control these non cytopathic versions of the virus?

Or does everyone with these infections develop symptoms?
 

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Messages
263
Note: this intracellular enterovirus infection found inside cells, and comprising a mixture of positive single-stranded RNA, negative single-stranded RNA and double-stranded RNA, goes by number of names, including the: non-cytolytic enterovirus, non-cytopathic enterovirus, terminally-deleted enterovirus, and defective enterovirus.

Dr Chia has explained in his video presentations that this process of two strings of single stranded RNA combining together to form one string of double-stranded RNA is actually a reversible process: as I understand, it is thought that the double-stranded RNA can also split apart again, and revert back to two strings of single stranded RNA again.

Dr Chia describes this enterovirus double-stranded RNA as the the "seeds" of this non-cytolytic intracellular infection. Seeds are very hardy, and you can destroy a plant, but it can regrow again from its hardy seeds. Likewise, the double-stranded RNA is very hardy, and may be involved in the spread of these non-cytolytic infections from cell to cell.


In terms of manufacturing viral proteins inside the cell, I believe only the positive single-stranded RNA can be used to do this. The double-stranded RNA is hardy, but I don't think this can used to express and manufacture viral proteins.

There is a thread here about how non-cytolytic enteroviruses infections may spread from cell to cell.


Note that you cannot detect non-cytolytic enteroviruses infections using antibody titer testing. Antibody titers are a indication of the amount of viral particles in the blood; but non-cytolytic enteroviruses are not found in the blood, but within human cells.

In fact in both ME/CFS and coxsackievirus B myocarditis, you can detect enteroviral RNA, but you often fail to detect any viral particles. Initially researchers found this very mysterious; but once non-cytolytic enteroviruses were discovered, they explained these findings: the enteroviral RNA found even in the absence of any viral particles actually likely comes from the non-cytolytic virus.


A slide from Dr Chia detailing the non-cytolytic virus (single and double stranded RNA):
View attachment 8458

"Dr Chia describes this enterovirus double-stranded RNA as the the "seeds" of this non-cytolytic intracellular infection. Seeds are very hardy, and you can destroy a plant, but it can regrow again from its hardy seeds. Likewise, the double-stranded RNA is very hardy, and may be involved in the spread of these non-cytolytic infections from cell to cell."

I think that is why Chia keeps people on Oxymatrine for 2 years or some times longer - "as relapses are very common with this"

@Hip I gave my Doctor a copy of the transcript you sent me(from youtube)and he has arranged for a couple of his other CFS/ME patients to be tested through EV Med for Enterovirus. I do not think that would have happened with out your assistance, so thanks :thumbsup:
 

Hip

Senior Member
Messages
17,824
Are some peoples immune systems able to kill off or keep under control these non cytopathic versions of the virus?

Or does everyone with these infections develop symptoms?

Good question. I don't think there is enough research data on non-cytolytic enterovirus infections to answer it though.

There needs to be a lot more research into non-cytolytic enteroviruses, not just for ME/CFS, but for the sake of several other diseases. Coxsackievirus B causes or is linked to ME/CFS, myocarditis, pericarditis, cardiomyopathy, pancreatitis, type 1 diabetes and polymyositis. So non-cytoapthic infections could well play a major role in all of these diseases. Why is the research on non-cytolytic enteroviruses so slow?

Here are a few quotes from Dr Chia study, the role of enterovirus in chronic fatigue syndrome:

Chia suggests non-cytolytic enteroviruses may avoid being destroyed by hiding in cells that the immune system goes softly-softly on (immunologically privileged cells):
The paradox remains, however, that despite an ongoing immune response, these viral RNA infected cells are not eradicated. It is possible that viruses hide in long living, immunologically privileged cells, including but not limited to, macrophages, muscles, myocardial cells, and neurones.


Chia points out the need to find reliable methods of detecting non-cytolytic enteroviruses:
To overcome the technical difficulties associated with the enteroviral RNA detection assay, because a reliable and reproducible measurement of cell associated viral RNA will provide a marker for antiviral treatment and provide conclusive evidence of chronic infection.



Chia thinks the immune system is capable of destroying non-cytolytic enteroviruses in their single stranded RNA form; but the immune system cannot easily destroy non-cytolytic enteroviruses in the double stranded RNA form.

So even if the immune system destroys all the non-cytolytic enterovirus single stranded RNA in our cells, this non-cytolytic infection will soon grow back again from its double stranded RNA "seeds."
 
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halcyon

Senior Member
Messages
2,482
Interesting link, thanks @Emootje. I recall there was a thread here a while back where a lot of people agreed they felt better when they didn't eat.

@knackers323 I have heard of people using infrared saunas for that. I have no idea if it's actually helpful or not.
 

knackers323

Senior Member
Messages
1,625
@halcyon I cannot make heads or tails out of the study in that link. Could you briefly tell me what it says about not eating and feeling better? Thanks
 

halcyon

Senior Member
Messages
2,482
If I understand the paper correctly, they found that activation of Akt (also known as protein kinase B) was necessary for CVB3 replication and by blocking activation they could interfere with viral replication. Insulin is also known to activate Akt, so perhaps by limiting insulin (by fasting) you could limit activation of Akt and interfere with viral replication. It's an interesting thought but who knows if it would actually have an effect or not.
 

halcyon

Senior Member
Messages
2,482
I've been interested in the possibility that elevated prostaglandin E2 could be playing a role in this disease. It seems that a lot of viruses induce COX-2 expression and thus PGE2 release. I've only found papers specifically stating that EV71 does it, but if one enterovirus can do it, it seems a good assumption that the others might as well. If I'm reading the science right, it seems COX-2 expression might be used by viruses as a countermeasure to evade immune response. PGE2 has been shown to inhibit interferon production and interfere with macrophage activity.

There are a number of interesting threads here on PGE2. I came across this one where the original poster claimed to have improvement of viral titers (HHV6 in his case) while taking Celebrex (a prescription COX-2 inhibitor) and Arbidol (an antiviral that also stimulates interferon release and macrophage activity). I wonder if a similar synergy could be achieved by taking a weaker, natural COX-2 inhibitor together with Equilibrant.

@Hip posted a good list of natural COX-2 inhibitors in the thread I referenced above. I picked the first one that I was already a little familiar with, curcumin, and started reading. Unfortunately, according to some of the information summarized on this page, it looks like curcumin might have anti-th1 effects which wouldn't be helpful here. The next natural COX-2 inhibitor that interests me is quercetin, and in fact the Enterovirus Foundation lists quercetin on their alternative treatment page.

I was curious if anyone here had used quercetin together with Equilibrant. I recognize that COX-2 inhibition is a bit of a scorched earth approach but it seems like excess PGE2 probably isn't doing us any favors either.
 

Hip

Senior Member
Messages
17,824
@halcyon
Dr William Pridgen has been running a study on fibromyalgia patients using COX-2 inhibitor drugs to fight herpes simplex infections (he thinks herpes simplex may underpin fibromyalgia).

Dr Pridgen found that combining a regular herpes simplex antiviral (like acyclovir, valacyclovir or famciclovir) with a COX-2 inhibitor drug (like celecoxib, diclofenac or meloxicam) has a far greater antiviral effect against herpes simplex.

Indeed, this study found that when both COX-1 and COX-2 were inhibited simultaneously, pseudorabies virus yields were dramatically reduced, with greater than a 200,000-fold reduction. (Note pseudorabies virus is similar to herpes simplex). COX-2 inhibitors also display antiviral effects against cytomegalovirus. Propolis is a potent natural COX-2 inhibitor, but has little effect on COX-1.


However, this study (full paper here) on coxsackievirus B3 myocarditis found that by blocking IL-17A, which greatly increases COX-2 and PGE2, this actually protected against myocardial injury, and led to marked reductions in coxsackievirus B3. Thus COX-2 and PGE2 may have an antiviral effect against CVB.

So while reducing COX-2 is good for fighting HSV and CMV infections, it may potentially make CVB infections worse.
 

Hip

Senior Member
Messages
17,824
I notice that a recombinant version of the dicer enzyme is available. Since dicer destroys the viral dsRNA "seeds" that Dr Chia thinks spread and maintain the viral RNA infection (ie, the non-cytolytic infection) in ME/CFS patients, I wonder if taking recombinant dicer as a drug would help destroy this viral dsRNA, assuming it is safe to do this.

The only dsRNA that exists in the human body comes from viruses; dsRNA is not produced as part of normal bodily functioning. Therefore, in this respect, dicer should not interfere with normal bodily function. Though dicer does have other functions in the body, which taking supplemental dicer may interfere with.


Note however that viral dsRNA is located inside human cells, so even if it were safe to take recombinant dicer, the question is, would this enzyme be able to cross the cellular membrane an enter into the cell, where it should destroy the dsRNA.

There may be ways to get dicer to enter into cells, if it didn't do so by itself. If you look at the way the antiviral drug DRACO works, this drug comprises two proteins molecularly bonded together: the first protein is designed to be attracted to viral dsRNA (since nearly all viral infections generate dsRNA inside infected cells), and the second protein is one which causes the infected cell to kill itself (the protein triggers cellular apoptosis).

One could conceive of a drug similar to DRACO, that would comprise the enzyme dicer bonded to a protein that is attracted to viral dsRNA. Such a drug might seek out and destroy all these nasty viral dsRNA "seeds" in an ME/CFS patient.
 
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Hip

Senior Member
Messages
17,824
Another interesting angle on non-cytolytic enteroviral infections is that these infections only occur in quiescent cells.

A quiescent cell is one that is not dividing and reproducing itself. Cells can be of the quiescent type, or the rapidly dividing and reproducing type.

Liver cells are an example of rapidly dividing cells: liver cells are always dividing and reproducing. You never really get non-cytolytic enteroviral infections in liver cells, because these infections cannot really exist in rapidly dividing cells.

Examples of quiescent cells are: neurons and muscle cells. These are cells in which non-cytolytic enteroviral infections can be created.

The reason that non-cytolytic infections only really occur in quiescent cells is because these cells lack a certain factor important for positive single-stranded RNA replication. So in these quiescent cells, not enough positive single-stranded RNA is produced. This then leads to the situation where, rather than having 100 times more positive strand RNA than negative strand RNA, you instead get equal amounts of each, which then leads to the formation of lots of these dsRNA "seeds" in the cell, as a result of all these positive and negative strands joining together, and combining to form dsRNA.


So if it were possible to increase that certain factor (I don't know its name) in quiescent cells, this might prevent the shortage in positive single-stranded RNA production, and thus return the ratio of positive to negative strand RNA production to 100:1, and thereby prevent the creation of these dsRNA "seeds" in the cell — seeds which are thought to play a major role in enterovirus-associated ME/CFS.
 
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halcyon

Senior Member
Messages
2,482
@halcyon
Dr William Pridgen has been running a study on fibromyalgia patients using COX-2 inhibitor drugs to fight herpes simplex infections (he thinks herpes simplex may underpin fibromyalgia).

Dr Pridgen found that combining a regular herpes simplex antiviral (like acyclovir, valacyclovir or famciclovir) with a COX-2 inhibitor drug (like celecoxib, diclofenac or meloxicam) has a far greater antiviral effect against herpes simplex.

Indeed, this study found that when both COX-1 and COX-2 were inhibited simultaneously, pseudorabies virus yields were dramatically reduced, with greater than a 200,000-fold reduction. (Note pseudorabies virus is similar to herpes simplex). COX-2 inhibitors also display antiviral effects against cytomegalovirus. Propolis is a potent natural COX-2 inhibitor, but has little effect on COX-1.


However, this study (full paper here) on coxsackievirus B3 myocarditis found that by blocking IL-17A, which greatly increases COX-2 and PGE2, this actually protected against myocardial injury, and led to marked reductions in coxsackievirus B3. Thus COX-2 and PGE2 may have an antiviral effect against CVB.

So while reducing COX-2 is good for fighting HSV and CMV infections, it may potentially make CVB infections worse.
It never is simple, is it? Quercetin has shown potent antiviral effects in vitro, the COX-2 inhibition it causes must be fairly weak. Either that or the antiviral effects are enough to make it not matter.
 

halcyon

Senior Member
Messages
2,482
I notice that a recombinant version of the dicer enzyme is available. Since dicer destroys the viral dsRNA "seeds" that Dr Chia thinks spread and maintain the viral RNA infection (ie, the non-cytolytic infection) in ME/CFS patients, I wonder if taking recombinant dicer as a drug would help destroy this viral dsRNA, assuming it is safe to do this.

The only dsRNA that exists in the human body comes from viruses; dsRNA is not produced as part of normal bodily functioning. Therefore, in this respect, dicer should not interfere with normal bodily function. Though dicer does have other functions in the body, which taking supplemental dicer may interfere with.


Note however that viral dsRNA is located inside human cells, so even if it were safe to take recombinant dicer, the question is, would this enzyme be able to cross the cellular membrane an enter into the cell, where it should destroy the dsRNA.

There may be ways to get dicer to enter into cells, if it didn't do so by itself. If you look at the way the antiviral drug DRACO works, this drug comprises two proteins molecularly bonded together: the first protein is designed to be attracted to viral dsRNA (since nearly all viral infections generate dsRNA inside infected cells), and the second protein is one which causes the infected cell to kill itself (the protein triggers cellular apoptosis).

One could conceive of a drug similar to DRACO, that would comprise the enzyme dicer bonded to a protein that is attracted to viral dsRNA. Such a drug might seek out and destroy all these nasty viral dsRNA "seeds" in an ME/CFS patient.
Interesting idea. I'm still unclear on exactly how the whole RNAi cascade is supposed to work. One paper I was reading made it sound like the end result of RNase deployment in a cell is apoptosis. If that were the case this probably wouldn't be very safe.
 

halcyon

Senior Member
Messages
2,482
Another interesting angle on non-cytolytic enteroviral infections is that these infections only occur in quiescent cells.
Is this true though? I don't believe the cells that Chia finds dsRNA in inside the stomach tissue are quiescent.