Could Crippled Herpesviruses Be Contributing to ME/CFS?

[Cort]

Given the ubiquity of herpesviruses, the common infectious trigger in ME/CFS and the fact that once you're infected with them - you're infected for life - it's no surprise that researchers have been interested in herpesviruses and ME/CFS for decades.

An NIH-funded Ohio State University team, though, believes most herpesvirus research is barking up the wrong tree. If they're right - and the evidence suggests they may be - you can throw out all the viral load studies.

Their finding - a protein the virus releases when it partially reactivates and then gets squished by the immune system - could help explain why viral loads may not matter.

This team has slowly but steadily studying this aspect in ME/CFS and other diseases for over a decade.

http://simmaronresearch.com/2018/11...ting-chronic-fatigue-syndrome-mecfs-diseases/

 

[Jackb23]

Go bucks!

 

[pattismith]

EBV can be deleterious to cell even when latent (no lytic replication and no abortive replication),
as research have shown it in Lymphoma and Gastric carcinoma EBV associated.

 

[Hip]

An NIH-funded Ohio State University team, though, believes most herpesvirus research is barking up the wrong tree. If they're right - and the evidence suggests they may be - you can throw out all the viral load studies.

Nice article, Cort. Very interesting.

It's pleasing to see the ideas of the late Dr Martin Lerner — that abortive herpesvirus infections (rather than regular productive herpesvirus infections) are a cause of ME/CFS — have not been abandoned, but are still being activity researched in Ohio.

I wrote a post on Lerner's abortive herpesvirus theory of ME/CFS here.


Abortive infections occur when a virus enters a cell type which has an internal environment that does not allow the virus to fully replicate itself. Thus the virus in these cells keeps trying to replicate, but never succeeds.

Normally when a virus succeeds in replicating, the newly-created viral particles burst out of the cell, thereby killing the cell, and that's the end of the story for that infected cell. But in abortive infections, the virus keeps trying to replicate itself, (and makes various viral proteins like dUTPase in the process), but never succeeds; so the viral infection goes on forever in that cell, and the cell is not killed.

 

[Wonkmonk]

so the viral infection goes on forever in that cell, and the cell is not killed.

Wasn't it Dr Lerner's theory that at some point these cells go into apoptosis? (thereby possibly spreading viral particles and infecting new cells or leading to immune system overactivation)

 

[Hip]

Wasn't it Dr Lerner's theory that at some point these cells go into apoptosis?

Yes, I think that's right. Though my understanding is that abortive infection is a long lingering process in a cell, not the very rapid process that you get with normal productive infection, where virus enters a cell, replicates and then kills the cell by lysis within a day.

In AIDS, the HIV virus infects CD4 cells in an abortive manner. So HIV lingers in these CD4 cells as an abortive infection, not a productive one. But as we all know, in untreated HIV the CD4 cell counts slowly diminish over the years. This was once thought to be due to apoptosis from this abortive infection, but I read one study which said the CD4 cell death was mostly due to pyroptosis (cell death due to inflammatory effects), though apoptosis does also contribute to CD4 cell death in AIDS.

 

[Wonkmonk]

So HIV lingers in these CD4 cells as an abortive infection, not a productive one.

It seems HIV also has a mechanism to spread directly from one cell to an adjacent cell.

https://www.newscientist.com/articl...-most-cells-by-a-method-overlooked-for-years/

This may be a similar to the mechanism you described for the spread of non-cytolytic enterovirus:

https://forums.phoenixrising.me/ind...roviruses-may-spread-from-cell-to-cell.19597/

This might be an explanation for why CFS is progressing very slowly in some patients.

 

[junkcrap50]

Is dUPTase unique to EBV? Does it exist in CMV? Can any virus have a abortive non-lytic infection?

 

[Hip]

Is dUPTase unique to EBV? Does it exist in CMV?

No it's not unique to EBV.

Can any virus have a abortive non-lytic infection?

I would guess any virus can create an abortive infection, if it infects non-permissive cells.

 

[Iritu1021]

I agree that latent viral infections might be the underlying issue in CFS as well as most other conditions but it seems that the direct link to dUPTase is rather weak at this point. It might be simply a detectable marker of the viral presence. To me, personally, it seems that viruses are more likely to cause problems by interfering with cellular signaling and/or neurotransmission (either through neuroreceptor or secondary messenger expression modification by the viral proteins).

Here's a quote from the book on intracellular calcium:

"Eukaryotic viruses affect cell metabolism and can exploit, hijack, or disrupt the Ca2+ signaling system in order to take over the biochemistry of a cell, and replicate. Many viruses interfere with normal Ca2+ signaling, involving effects on Ca2+ channels in the plasma membrane, and Ca2+movement in the ER and mitochondria. Viruses can induce cytosolic free Ca2+ signals through store operated calcium entry, voltage-gated Ca channels, and metabotropic Ca2+ channels. They can also form ion channels and pores from viroporin proteins. Viruses can affect gene expression and replication through activation of Ca2+ calmodulin kinases (CaMKs) and calreticulin. The alteration in Ca2+ signaling either enhances viral replication or prevents the cell going into apoptosis, which would otherwise leave the virus stranded mid-stream. Intracellular Ca2+ also plays a crucial role in the immune system.

Herpes simplex activates a rapid cytosolic Ca 2+ transient through the production of IP3. This is necessary for the activation of focal adhesion kinase.

Similarly, coxsackievirus B activates phospholipase C (PLC) in endothelial cells, IP3 releasing Ca2+ from the ER, thereby activating SOCE.

Epstein-Barr virus immortalizes lymphocytes, altering Ca2+ signaling by increasing ER Ca2+, affecting the resting cytosolic free Ca2+ and SOCE. LMP-1 is a key EBV protein in this process, increasing SOCE through the expression of STIM and Orai. EBV also reduces the release of cytochrome c from mitochondria, by interfering with the voltage-dependent anion protein 2."

 

[Hip]

I agree that latent viral infections might be the underlying issue in CFS as well as most other conditions but it seems that the direct link to dUPTase is rather weak at this point.

An abortive viral infection is not the same as a virus in its latent state. Different things.

 

[olegsel]

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS characterized by progressive demyelination and disability. Epstein-Barr (EBV) virus has been implicated in the pathogenesis of MS, as high anti-EBV titers have been reported in patients with MS. In this episode, Michael Pender and Rajiv Khanna discuss the results of an open-label, dose escalation trial designed to evaluate the safety and efficacy of adoptively transferred in vitro-expanded EBV-specific T cells for patients with progressive MS. Clinical improvement was seen 7 of the 10 patients, with the greatest benefit for patients that received T cells with strong EBV reactivity. The results from this initial trial indicate that the EBV-specific adoptive T cell therapy is well tolerated and support further investigation of this approach in efficacy trials.
https://neurosciencenews.com/immunotherapy-ms-10238/

one more confirmation

 

[Belbyr]

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS characterized by progressive demyelination and disability. Epstein-Barr (EBV) virus has been implicated in the pathogenesis of MS, as high anti-EBV titers have been reported in patients with MS. In this episode, Michael Pender and Rajiv Khanna discuss the results of an open-label, dose escalation trial designed to evaluate the safety and efficacy of adoptively transferred in vitro-expanded EBV-specific T cells for patients with progressive MS. Clinical improvement was seen 7 of the 10 patients, with the greatest benefit for patients that received T cells with strong EBV reactivity. The results from this initial trial indicate that the EBV-specific adoptive T cell therapy is well tolerated and support further investigation of this approach in efficacy trials.
https://neurosciencenews.com/immunotherapy-ms-10238/

one more confirmation

very interesting

 

[Iritu1021]

An abortive viral infection is not the same as a virus in its latent state. Different things.

You're right, I should have said "non-lytic" infection.

 

[Belbyr]

Could this be why Ampligen seems to work in some preliminary CFS studies?

 

[olegsel]

Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Abstract
BACKGROUND AND MAIN TEXT:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies.
CONCLUSIONS:
This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.

https://www.ncbi.nlm.nih.gov/pubmed/30285773