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Regular Enteroviruses and Non-Cytopathic Enteroviruses

Jonathan Edwards

"Gibberish"
Messages
5,256
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:

It's an interesting story but it looks pretty speculative to me. Certainly the link to ME is entirely speculative.
 

Hip

Senior Member
Messages
17,824
It's an interesting story but it looks pretty speculative to me. Certainly the link to ME is entirely speculative.

When you say it looks speculative, do you mean the idea that terminally deleted viruses are playing a causal role in myocarditis and ME/CFS is speculative? Or that it is speculative that these terminally deleted viruses are present in myocarditis and ME/CFS?

Certainly it would be nice if we could have more investigation into terminally deleted enteroviruses, to establish their degree of involvement (if any) in various enterovirus-associated diseases, such as CVB myocarditis, ME/CFS and type 1 diabetes.

There is evidence for terminally deleted enterovirus involvement in ME/CFS: Dr John Chia in his 2008 study (full paper here) showed that normal lytic enteroviruses are not always found in ME/CFS patients, in spite of the fact that enteroviral RNA can be detected. So this state of affairs, like the CVB myocarditis case, suggests there is an infection with terminally deleted enteroviruses, and that this might be playing a causal role.

Also, Cunningham et al in 1990 (full paper here) found that in the enteroviral RNA isolated from the tissues in ME/CFS patients, there was much more negative stand RNA than is normally found in normal lytic enterovirus infections. Normally in lytic enterovirus infections, you find a 100 times more positive strand RNA than negative strand RNA.

But Cunningham et al found that in ME/CFS patients, there was roughly equal amounts of positive and negative strand enteroviral RNA; this is characteristic of non-cytolytic, terminally deleted enterovirus infections.



After an acute enterovirus infection has been cleared up by the immune system, and no more viral particles can be found, an intracellular non-cytolytic enterovirus infection may remain, and this ongoing chronic non-cytolytic infection may turn out to provide an explanation of why we observe continued chronic immune attack / inflammation (even if it is not true autoimmunity) in organs or cells hit by an acute enterovirus infection.
 
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halcyon

Senior Member
Messages
2,482
Certainly the link to ME is entirely speculative.
The work of Tracy and Chapman isn't really about the link to ME. They have just clearly and definitively demonstrated that enteroviruses can persist in a chronic active form and have figured out how they do it. There is decades of research on the link to ME, from multiple countries, going back to Dr. Ramsay himself. With respect, I don't think you can make such a definitive statement if you haven't read all of the research.

I developed ME after an acute echovirus 30 infection that turned chronic. The link is very real to me.
 

Hip

Senior Member
Messages
17,824
Just came across this new study which found that the anti-fungal drug itraconazole (Sporanox) is a broad-spectrum antiviral for enteroviruses, including coxsackievirus.

Itraconazole inhibits viral RNA replication, so this may have effects against non-cytolytic enteroviruses as well.

I looked back at my personal notes, and saw that I actually tried itraconazole 100 mg daily for 2 whole months (as an anti-fungal experiment), back in 2007. However, at this dose level, it did not appear to make any noticeable improvements to my ME/CFS symptoms.

It says here that 600 mg a day is approaching the maximum dose of itraconazole. Itraconazole is a well-tolerated drug, so it should be possible to take such high doses without too much risk of side effects. However, such high doses would work out to be quite expensive.
 

Hip

Senior Member
Messages
17,824
What role do cytokines play into these conditions?

If you search this forum for Michael VanElzakker's theories on how the sickness behavior cytokines IL-1beta, TNF-alpha and IL-6 may underpin ME/CFS, you'll find lots of info on the possible role of cytokines in ME/CFS.
 
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Hip

Senior Member
Messages
17,824
Two Differing Models of Non-Cytolytic Enteroviruses

I came across this interesting study by Tam and Messner, which suggests that the dsRNA found in persistent non-cytolytic enterovirus infections does not involve any genetic alternations (5' terminal deletions) of the enteroviral RNA genome, contrary to what Profs Tracy and Chapman et al have found.

Tam and Messner found that the dsRNA of non-cytolytic enterovirus infection consists of regular enterovirus RNA (ie, wild-type enterovirus), having a full intact viral genome.



Thus there appear to be two competing views on the nature of these non-cytolytic enteroviruses: Tracy and Chapman's research found that non-cytolytic enteroviruses have genetic deletions in the 5' region of the enterovirus genome; whereas Tam and Messner found that the dsRNA of non-cytolytic enteroviruses has an intact genome, without any deletions.

This paper talks about these two views:
Data from other CVB models suggest that, contrary to the mechanism proposed by the above studies [by Tracy and Chapman et al], virus persistence is facilitated not by genetic alterations in the virus that give rise to replication-defective forms but by the genetic stability of double-stranded complexes of wild-type viral RNA.

Data from a number of laboratories which have identified a 1/1 ratio of positive- to negative-strand viral RNA genome during persistence in the heart would fit well with the model proposed by Tam and Messner.



I am not sure if either view makes much difference in terms of considerations of how this dsRNA infection in human cells might be eradicated.
 
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