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Regular Enteroviruses and Non-Cytopathic Enteroviruses

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
The real issue with enteroviruses is us is there is probably little or no replication. Blocking replication may not have a big effect. The two tissue infection life cycles for enteroviruses so far identified involve minimal replication. There may be some, but its the presence of the virus itself that is likely to be problematic. On the other hand if these substances block viral protein synthesis, then stopping our cells from pumping out viral proteins (an hypothetical issue) could be a good thing.
 

Hip

Senior Member
Messages
17,824
The real issue with enteroviruses is us is there is probably little or no replication. Blocking replication may not have a big effect.

Quite possibly true. With both cytopathic and non-cytopathic enterovirus infections going on simultaneously, an antiviral may reduce the cytopathic infection, but may not touch the non-cytopathic infection.


I think a possibly useful model to study the efficacy of coxsackievirus B antivirals might be chronic coxsackievirus B myocarditis.

OK, coxsackievirus B myocarditis is not ME/CFS, but it does involve a long term, smoldering infection with coxsackievirus B, and Dr John Chia has also found long term, smoldering enterovirus infections in ME/CFS patients. Chronic coxsackievirus B myocarditis also involves a non-cytopathic enterovirus infection — an infection believed to play a role in ME/CFS.

In murine models, coxsackievirus B myocarditis leads to heart muscle lesions and mortality. Any compound that reduces the coxsackievirus B viral load or coxsackievirus B induced inflammation in the mouse hearts tends to reduce mortality rates and lesions. Reduced mortality rates/lesions are thus a way to gauge the potency of a coxsackievirus B antiviral for myocarditis.

This study for example found that a 3C protease inhibitor reduced murine myocarditis mortality rates. I wonder if that same 3C protease inhibitor might help ME/CFS patients.

I compiled a list of anti-enterovirus compounds HERE.
 

globalpilot

Senior Member
Messages
626
Location
Ontario
The real issue with enteroviruses is us is there is probably little or no replication. Blocking replication may not have a big effect. The two tissue infection life cycles for enteroviruses so far identified involve minimal replication. There may be some, but its the presence of the virus itself that is likely to be problematic. On the other hand if these substances block viral protein synthesis, then stopping our cells from pumping out viral proteins (an hypothetical issue) could be a good thing.

What are the 2 life cycles you refer to Alex ?
Dr Chia examines endoscopy of the stomach - I presume epithelial cells and not muscle. I'm having a hard time how the virus would persist here without replication - otherwise I think the viral load would reduce over time by apoptosis.
I sure hope we can get some more clarity of this soon.
 

globalpilot

Senior Member
Messages
626
Location
Ontario
Anyone have access to this, please:

Identification of a Series of Compounds with Potent Antiviral Activity for the Treatment of Enterovirus Infections.

The authors identified a group of compounds that have potent antiviral action against human rhinovirus, coxsackievirus, poliovirus and enterovirus-71, and say these compounds work by blocking viral replication.

ME/CFS is strongly linked to persistent enterovirus infection in the body (particularly coxsackievirus B and echovirus), so it would be interesting to learn which compounds were identified in this study as having potent anti-enteroviral effect.

A poster of their research can be found here (but the poster unfortunately does not name the antiviral compounds).

My local university subscribes to that journal. I'll go there soon and get it.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
What are the 2 life cycles you refer to Alex ?
Dr Chia examines endoscopy of the stomach - I presume epithelial cells and not muscle. I'm having a hard time how the virus would persist here without replication - otherwise I think the viral load would reduce over time by apoptosis.
I sure hope we can get some more clarity of this soon.

There was an issue of IiME magazine a couple of years ago. Enteroviruses can lose part of their DNA, and adopt a different lifecycle to the lytic model. This could be confirmed by sequencing the virus. Nobody at that time seems to have understood why they do this. Both can replicate, but in a very very limited fashion. The first causes very very slow replication, not slash and burn as found in lytic lifecycles. The other cannot replicate unless you have a coinfection of a similar viral strain, but it can make proteins, and these might be toxic. I have limited computer use at the moment or I would get you a link. I have a bad computer virus and am about to format my hard drives and reinstall windows.
 

globalpilot

Senior Member
Messages
626
Location
Ontario
thanks Alex.
I did read that article in the IiME a couple of days ago.
He said that this slow growing version would only survive in non-dividing cells.
But Dr Chia found enterovirus in teh stomach and he told me that the biopsy sample doesn't include the muscles.
So he is finding the virus in normal dividing cells.
I might set up another consult with Dr Chia and get more answers.

I hope your computer gets sorted.
 

Hip

Senior Member
Messages
17,824
Enteroviruses can lose part of their DNA, and adopt a different lifecycle to the lytic model.

Yes, these enteroviruses that lose part of their RNA — and thus transform into a different form of the virus — are called by a number of names, including:

Non-cytopathic enteroviruses,
Non-cytolytic enteroviruses,
Defective enteroviruses,
Terminally-deleted enteroviruses.

All these names refer to the same virus: this enterovirus that has lost a small portion of its RNA.

(For a Google search on all these terms, click HERE).

In chronic enterovirus infections, it seems you get a combination of regular enteroviruses and these non-cytopathic enteroviruses both infecting the host.
 
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voner

Senior Member
Messages
592
enterovirus folks, I am a patient of Dr. Chia's and After many tries, I finally got some ARUP enterovirus test results... Anyone want to shoot and interpretation? They were not abnormal, except for this .....

Here is the anomalous result:


Echovirus antibody type 6 1:80 "abnormal" (less than 1:10)


ARUP Says that titers greater than or equal to 1:80 may indicate past or current infection.

I have not spoken to Dr. Chia about the results, yet.
 

Hip

Senior Member
Messages
17,824
Does anyone know the exact way that Equilibrant is supposed to work against enteroviruses? Or rather, Oxymatrine?
The theory is that oxymatrine increases the Th1 mode of the immune response, and decreases the Th2 mode. It is the Th1 mode which is antiviral, so this helps fight enteroviral infections.
 

Hip

Senior Member
Messages
17,824
voner
The Enterovirus Foundation website says that titers of 1:320 and higher in those ARUP tests tend to indicate a current active infection.

So your result of 1:80, which is lower than 1:320, indicates you have not got an active infection.

Note on Titer Figures
Titers fall in the sequence: 1:10 ... 1:20 ... 1:40 ... 1:80 ... 1:160 ... 1:320 ... 1:640 ... 1:1280 ... etc

Or else into the sequence: 1:8 ... 1:16 ... 1:32 ... 1:64 ... 1:128 ... 1:256 ... 1:512 ... 1:1024 ... etc

The higher numbers towards the right of these sequences indicate higher levels of infection. So for example, a result of 1:640 indicates more viral activity than a result of 1:80.
 

ttt

Senior Member
Messages
101
Location
Santa Monica, CA
Forgive me if this question is really ignorant, but what is the difference between an enterovirus and a regular virus? I have an appointment for a consult with Dr. Chia in December, and in the meantime, I'm trying to understand more about enteroviruses. Thanks!
 

Hip

Senior Member
Messages
17,824
Forgive me if this question is really ignorant, but what is the difference between an enterovirus and a regular virus?

The distinction being made in this thread is between regular enteroviruses, and the noncytopathic enteroviruses. These are two different forms of the same virus.

When you first catch an enterovirus, usually as a respiratory infection, you will catch the normal, regular form of this virus. However, once in your body as a chronic infection, some of these normal enteroviruses can change into a new form of the virus called a noncytopathic enterovirus.

The noncytopathic enterovirus derives from the original normal enterovirus you caught, but it acts differently to the normal enterovirus.

The main difference between a normal enterovirus and a noncytopathic enterovirus is that the latter live inside human cells as a chronic intracellular infection, whereas the former live mostly outside human cells, and just enter the cell for replication purposes.

Note that enterovirus is an umbrella term: the term enterovirus is a genus that covers a series of closely related viruses. Viruses that come under the enterovirus umbrella include: coxsackievirus A, coxsackievirus B, echovirus, poliovirus, and certain viruses like enterovirus-71. Usually in the case of ME/CFS, the specific enteroviruses involved are coxsackievirus B and echovirus.

You can learn more about enteroviruses here:

Non-cytolytic / non-cytopathic (defective) enterovirus — MEpedia

Enteroviruses

Non-Polio Enterovirus Infection: About Non-Polio Enteroviruses - CDC

Enterovirus Foundation
 
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alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
As a technical point, viruses are only alive inside cells, as they have no machinery to replicate, repair, metabolize etc, they use cellular mechanisms. The thing is that noncytopathic viruses do not usually lyse the cell and release millions of copies of themselves, so blood levels of virus are very very low. Regular lytic lifecycle viruses make millions of copies, explode the cell, then get released into the blood. This is what you see on a blood viral titre test. I suspect though that 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.

If the immune system is responding properly you should also see lots of antibodies to the virus from about week two of the acute infection, or week one if you have had that virus before. Those antibodies are what is measured on an antibody titre test. The antibody tests are indirect, there is no way to be sure they are to exactly 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.

Also it is my understanding that for enteroviruses there are two different noncytopathic forms currently known ... so you could wind up with three infections from the initial enterviral trigger, one acute infection that should resolve fast, and two smoldering infections that appear to be for life unless they can be treated.

The only way to be sure if noncytopathic viruses are cleared is not by any sort of blood test, but by biopsy.
 

alex3619

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

Endomyocardial biopsy
Molecular biology (PCR)
Enterovirus 15 0
0.001
Adenovirus 7 0
0.05
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.