Early Growth Response Gene Upregulation in Epstein–Barr Virus (EBV)-Associated Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

nerd

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This isn't the newest study of all but it hasn't been discussed yet and I think it deserves a separate post. It's a review of the existing evidence on latent EBV pathology in CFS/ME.

Author: Jonathan Kerr
Published: 26 October 2020
doi: 10.3390/biom10111484

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic multisystem disease exhibiting a variety of symptoms and affecting multiple systems. Psychological stress and virus infection are important. Virus infection may trigger the onset, and psychological stress may reactivate latent viruses, for example, Epstein–Barr virus (EBV). It has recently been reported that EBV induced gene 2 (EBI2) was upregulated in blood in a subset of ME/CFS patients. The purpose of this study was to determine whether the pattern of expression of early growth response (EGR) genes, important in EBV infection and which have also been found to be upregulated in blood of ME/CFS patients, paralleled that of EBI2. EGR gene upregulation was found to be closely associated with that of EBI2 in ME/CFS, providing further evidence in support of ongoing EBV reactivation in a subset of ME/CFS patients. EGR1, EGR2, and EGR3 are part of the cellular immediate early gene response and are important in EBV transcription, reactivation, and B lymphocyte transformation. EGR1 is a regulator of immune function, and is important in vascular homeostasis, psychological stress, connective tissue disease, mitochondrial function, all of which are relevant to ME/CFS. EGR2 and EGR3 are negative regulators of T lymphocytes and are important in systemic autoimmunity.
 

Pyrrhus

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Thanks so much for posting this study which had been overlooked!

There have been many chicken-or-the-egg discussions regarding reactivation of herpesviruses and PEM.

I try to look at both sides here:
I could see it either way:
  • Herpesviruses have a complicated logic built into their genetics that is constantly surveying the cellular status to "decide" whether to reactivate. One example of this is the reactivation of herpesviruses in response to pro-inflammatory cytokines.[1] If a crash leads to cellular conditions favorable to the herpesvirus, then the crash could lead to reactivation of a herpesvirus.
or
  • Exertion is often accompanied by activation of the sympathetic nervous system. Activation of the sympathetic nervous system decreases the function of NK cells.[2][3] NK cells are the most potent immune cell for preventing reactivation of herpesviruses, for some reason.[3][4] So activation of the sympathetic nervous system by exertion might lead to reactivation of a herpesvirus, which might lead to the symptoms of a crash. One example of this is the outbreak of cold sores that some people experience in response to stressful episodes.
References:
[1] https://pubmed.ncbi.nlm.nih.gov/9475116/
[2] https://content.iospress.com/download/advances-in-neuroimmune-biology/nib006?id=advances-in-neuroimmune-biology/nib006
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144531/
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788305/
 

perrier

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Where is Dr Kerr these days? He is one of the most decent empathetic ME dr I have ever tun into. He wasn’t at the zoom conference I note. Does anyone know his whereabouts?