CFS: new findings about human herpesviruses (EBV, HHV-6)

[Th1please]

Full text/study: Biomolecules | Free Full-Text | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back! | HTML (mdpi.com)

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) is a chronic multisystem illness of unconfirmed etiology. There are currently no biomarkers and/or signatures available to assist in the diagnosis of the syndrome and while numerous mechanisms have been hypothesized to explain the pathology of ME/CFS, the triggers and/or drivers remain unknown. Initial studies suggested a potential role of the human herpesviruses especially Epstein-Barr virus (EBV) in the disease process but inconsistent and conflicting data led to the erroneous suggestion that these viruses had no role in the syndrome. New studies using more advanced approaches have now demonstrated that specific proteins encoded by EBV could contribute to the immune and neurological abnormalities exhibited by a subgroup of patients with ME/CFS. Elucidating the role of these herpesvirus proteins in ME/CFS may lead to the identification of specific biomarkers and the development of novel therapeutics.

 

[Pyrrhus]

Thank you so much for sharing!

There is also a discussion about the press release that followed this publication:
https://forums.phoenixrising.me/threads/ohio-state-dutpase-biomarker-announcement.82996/

(I guess the press release generated more news buzz than the actual paper!)

 

[Pyrrhus]

Oh, and just to let you know, some people like to title discussion threads about a specific publication with the full name of the publication. This way, it is easier for someone who is trying to find a specific publication in a search.

Although the full title is usually spelled out in the thread title, some people abbreviate "myalgic encephalomyelitis/chronic fatigue syndrome" to just "ME/CFS".


If you feel like doing this, this thread would then be titled:

ME/CFS: The Human Herpesviruses Are Back! (Ariza, 2021)


Hope this helps, and thanks again!

 

[Th1please]

Oh, and just to let you know, some people like to title discussion threads about a specific publication with the full name of the publication. This way, it is easier for someone who is trying to find a specific publication in a search.

Although the full title is usually spelled out in the thread title, some people abbreviate "myalgic encephalomyelitis/chronic fatigue syndrome" to just "ME/CFS".


If you feel like doing this, this thread would then be titled:

ME/CFS: The Human Herpesviruses Are Back! (Ariza, 2021)


Hope this helps, and thanks again!

Thanks for the info! Sorry about that.

It seems I can't edit my first post, there may be a timing for that. I'll be more careful for my next post

 

[gbells]

I think the suppression of EBV virions and antibodies by HHV-6 threw the researchers for a loop and they're finally starting to realize it. They still don't have any treatments for HHV-6.

https://www.mdpi.com/2218-273X/11/2/185/htm

While there have been sporadic reports in the literature concerning the potential role of HSV-1&2, HCMV, HHV-7, HHV-8 and VZV in ME/CFS such reports have not been validated. There have been also numerous studies attempting to link EBV and HHV-6 as potential triggers of ME/CFS. However, these studies provided conflicting data and resulted in Soto and Straus prematurely declaring that the evidence for herpesviruses involvement in ME/CFS was fading [10]. What are the reasons for this conclusion? Most of the initial studies linking ME/CFS to EBV were serological studies performed using the classical EBV antigens: Early antigen-diffuse pattern (EA-D), Early antigen restricted pattern (EA-R), viral capsid antigen (VCA) and Epstein-Barr Nuclear Antigen 1 (EBNA 1) [6,11,12,13,14,15,16,17,18,19,20]. Overall, these studies gave conflicting results. Recent studies using more advanced technologies such as peptide microarray [21] and suspension multiplex immunoassay [22] reported that the EBV anti-IgG response in ME/CFS patients was not significantly different than controls. In both studies there were small non-significant differences in IgG response to Epstein-Barr Nuclear antigen 3C (EBNA-3; EBNA 6) and in the Blomberg study to EA-D. These findings are consistent with numerous reports raising awareness to the fact that analyses of EBV serological data are complicated and thus, cautious interpretation is required. This is due to several factors including, but not limited to, the heterogeneity of the populations under study, the lack of case study definition, questions concerning the reliability and precision of the results obtained from different commercial laboratories as well as the lack of a demonstrated correlation between serological data and viral load indicating that classical serological data may be of limited use as an indicator of EBV reactivation [23].

A central concept regarding the biology of herpesviruses is that two distinct phases of viral gene expression exist either in latency or lytic replication where virus progeny are produced. However, there is accumulating data to suggest that, at least in the case of EBV, this central concept may be incorrect and that in vivo a third state exists: abortive lytic/leaky replication.

Prusty et al. [47] using an epithelial (U2OS) cell culture-HHV-6 latency model recently identified an early stage of HHV-6 reactivation, termed transactivation, characterized by the transcription of several viral small non-coding RNAs (sncRNAs) and the absence of increased viral replication. The data suggest that ALR might be occurring in HHV-6 infections. Furthermore, while the lack of complete/productive viral replication occurred in these cells, the cells gained partial function by viral genome transactivation and the investigators suggested that this might have clinical significance.

Several studies have demonstrated the presence of autoantibodies in patients with ME/CFS against numerous cellular components including anchorage molecules [89,90], heat shock protein 60 [91], human nuclear dUTPase [48], microtubule associated protein 2 [92], muscarinic cholinergic and β-adrenergic receptors [93,94] nuclear envelop protein lamin B1 [95], serotonin [96,97] and single and double stranded DNA [98], resulting in the hypothesis that ME/CFS may represent an autoimmune disease [99,100]. It has been suggested that EBV may be inducing the formation of autoreactive B cells through a molecular mimicry process with an EBV antigen and self-antigens [99,100]. However, studies to demonstrate whether or not EBV is inducing the formation of autoantibodies in patients with ME/CFS through a molecular mimicry mechanism are lacking [21,53]. Furthermore, studies to address B cell populations in patients with ME/CFS have provided conflicting information [51,101,102,103,104].

Neuroinflammation is a common feature of ME/CFS, affecting 85–90% of all patients, yet the underlying mechanism(s) responsible for the initiation and/or promotion of this process is largely unknown. Although neuroimaging studies have found structural and functional alterations in the brains of ME/CFS patients, there is limited evidence to suggest activation of astrocytes and microglia or widespread neuroinflammation in the brains of these patients [116]. Despite the fact that there are in vivo studies in mice suggesting the involvement of the NLRP3 inflammasome in the neuroinflammatory process [117,118] and a study in humans indicating metabolic and temperature abnormalities in the brains of patients with ME/CFS [119], studies to demonstrate the mechanism(s) by which neuroinflammation was induced as well as the consequences of this process are lacking.

A recent study [120] in a mouse model revealed that EBV dUTPase altered the expression of 34 genes with central roles in blood-brain-barrier (BBB) integrity (CGN, TJP2, RAPGEF6), fatigue (TCB1D1), pain (GCH1, GPR84), synapse structure (LIN 7b, SYNPO, RAB33A) and function (Egr1), as well as tryptophan, dopamine and serotonin metabolism (GCH1, DBH, DRD5, GRK6, KMO, Nr4a1, Slc6a3, SLC6a4, Th, Tph2) (Figure 3).

So now we have two mechanisms suggested for depression, neurotransmitter depletion and SITH1 protein production by HHV-6. That explains the ME depression and anxiety.

Very good paper overall.

 

[bensmith]

I hope they find some way to regulate our nuero inflam soon, it makes me crazy and is very painful.

 

[Pyrrhus]

It seems I can't edit my first post, there may be a timing for that. I'll be more careful for my next post

You may be able to change the title by choosing "Edit thread" as shown below:

I hope this helps!

 

[Aurelius]

Do they write something about countermeasures?

 

[Learner1]

@Th1please Thank you for spotting this and sharing. It well describes the many problems with the quality and accuracy of research to date. The significance, though, is a breakthrough for many ME/CFS patients. It's an article worth sharing with our doctors.

They still don't have any treatments for HHV-6.

Here are some.

https://hhv-6foundation.org/clinicians/hhv-6-treatment

 

[gbells]

@Th1please Thank you for spotting this and sharing. It well describes the many problems with the quality and accuracy of research to date. The significance, though, is a breakthrough for many ME/CFS patients. It's an article worth sharing with our doctors.



Here are some.

https://hhv-6foundation.org/clinicians/hhv-6-treatment

They don't eradicate the viruses just block reproduction. What good is that?