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Regular Enteroviruses and Non-Cytopathic Enteroviruses

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by alex3619, Aug 5, 2013.

  1. alex3619

    alex3619 Senior Member

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    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.
    merylg likes this.
  2. Hip

    Hip Senior Member

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    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.
    merylg likes this.
  3. globalpilot

    globalpilot Senior Member

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    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.
    vli likes this.
  4. globalpilot

    globalpilot Senior Member

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    My local university subscribes to that journal. I'll go there soon and get it.
    merylg, voner and vli like this.
  5. Hip

    Hip Senior Member

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    That will be great.
  6. alex3619

    alex3619 Senior Member

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    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.
    merylg likes this.
  7. globalpilot

    globalpilot Senior Member

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    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.
    merylg likes this.
  8. Hip

    Hip Senior Member

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    Yes, these enteroviruses that lose part of their RNA — and thus transform into a different sort of 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.

    Interestingly, the part of the RNA that these non-cytopathic enteroviruses lose is the part that encodes for the outer shell of the virus (the capsid, as it is called). This means that non-cytopathic enteroviruses can no longer make an outer shell. The outer shell of the virus of course houses the viral RNA or DNA. Without an outer shell to protect their RNA, these non-cytopathic enteroviruses cannot travel far in the blood or the environment to infect other cells in the body, or to infect other people, because the naked RNA of non-cytopathic enteroviruses would be quickly destroyed in the environment.

    However, there is some evidence that non-cytopathic enteroviruses can infect close by, adjacent cells by a mechanism which creates a bridge between two cells in proximity. This bridge (which is called a cellular protrusion) temporarily connects two adjacent cells, and this bridge may allow non-cytopathic enteroviruses to transit to and infect adjacent cells. So in this way, even the non-cytopathic enterovirus infection may spread.

    In this thread HERE I wrote up some details about these cell-to-cell cellular protrusion bridges, and how non-cytopathic enteroviruses may infect adjacent cells via these bridges.
    merylg and alex3619 like this.
  9. globalpilot

    globalpilot Senior Member

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    I'm so sorry. I want to the library.
    They have ACS Medicinal Chemistry but NOT ACS Medicinal Chemistry letters.

    GP
  10. Gypsy

    Gypsy Senior Member

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    Does anyone know the exact way that Equilibrant is supposed to work against enteroviruses? Or rather, Oxymatrine?
    merylg and voner like this.
  11. voner

    voner Senior Member

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    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.
  12. Hip

    Hip Senior Member

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    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.
    heapsreal and merylg like this.
  13. Hip

    Hip Senior Member

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    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.

  14. voner

    voner Senior Member

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    hip,

    thank you.
    Hip likes this.
  15. globalpilot

    globalpilot Senior Member

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    Waverunner likes this.
  16. globalpilot

    globalpilot Senior Member

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  17. ttt

    ttt

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    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!
  18. Hip

    Hip Senior Member

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    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 — so that you now have two infections in your body for the price of one!

    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, whereas the former live mostly outside human cells. It is thought that both these two forms of enterovirus may be contributing to ME/CFS symptoms, but nobody knows for sure.

    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:

    Enteroviruses

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

    Enterovirus Foundation
    Little Bluestem likes this.
  19. alex3619

    alex3619 Senior Member

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    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.
    voner likes this.
  20. alex3619

    alex3619 Senior Member

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    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.

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