Epstein-Barr virus dUTPase induces neuroinflammatory mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

[Violeta]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525645/

Multiple reports, however, have suggested a role for Epstein-Barr virus (EBV), in particular, in ME/CFS but its potential role, if any, in the neuroinflammatory process has not been addressed. In support of this premise, studies by our group have shown that the EBV protein deoxyuridine triphosphate nucleotidohydrolase (dUTPase), induces anxiety and sickness behaviors in female mice.

A larger ME/CFS case/control cohort study further confirmed that a significant percentage of ME/CFS patients (30.91-52.7%) were simultaneously producing antibodies against multiple human herpesviruses-encoded dUTPases and/or human dUTPase.

Altogether, these findings suggest that EBV dUTPase protein may be involved in the neuroinflammatory process observed in ME/CFS. Thus, the aim of the present study was to determine whether the EBV dUTPase protein could contribute to neuroinflammation by altering the expression of genes involved with maintaining blood brain barrier (BBB) integrity and/or modulating synaptic plasticity.

 

[datadragon]

I posted some of this once before: the reactivation of multiple herpesviruses (EBV, HHV-6) and their production of dUTPase can elicit both humoral and cellular immune responses, including the hyperactivation of Th1 and Th17 in some patients with ME/CSF which has been in the literature for awhile. It does not appear to be the cause of the problem but is instead another downstream effect if immune function is compromised, the virus compromising the immune function, or stressed and viruses are allowed to reactivate adding additional fuel to the fire of the existing problem.

The reactivation of dormant viruses such as EBV and HHV-6 due to immune dysregulation and the activation of the interferon cascade, induction of the NLRP3 inflammasome, increased oxidative damage and lowered antioxidant defenses (the glutathione system and zinc), infection, neuro-inflammation including the brainstem, molecular mimicry and autoimmunity, and, of course, underlying genetic predisposition have been hypothesized as potential triggers of long COVID

EBV and HHV-6 are actually the most common immunotropic viruses which use latency after infection to hide from the immune system. EBV has infected more than 90% of the world’s population and more than 95% of healthy adults. HHV-6 is the collective name for the double-stranded DNA viruses HHV-6A and HHV-6B. More than 90% of humans are infected with HHV-6B within the first three years of life.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9967513/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142679/

A bit more from that article for those who want more detail: TLR2 is a type of receptor that is localized on the surface of immune cells and can form complexes with TLR1 or TLR6. A significant binding affinity exists between viral dUTPases (PAMPs) and TLR2. Although TLR2 is part of the innate immune response and is vital for the defense against viruses, its activation has been shown to be involved in various autoimmune diseases, including RA, Sjögren’s syndrome, MS, systemic sclerosis and systemic lupus erythematosus (SLE). This is because once engaged, TLR2 activates a signaling cascade that results in the production of proinflammatory cytokines that contribute to the development and progression of many disorders. For example, Ariza et al. demonstrated that through the engagement of the TLR2 homodimer, EBV-dUTPase induces the activation of NF-κB, which is a very strong proinflammatory mediator. Interestingly, HSV-2 and HHV-6A dUTPases also activated NF-κB after ligation with TKR2/1 heterodimer. Furthermore Ariza et al. showed that EBV, HHV-6 and other viral dUTPases are capable of activating different lymphocyte subpopulations and inducing the production of T-helper-1 (Th1), T-helper-17 (Th17), and other inflammatory cytokines such as IL-1β, IL-6, IL-8 and TNF-α

Viruses can trigger a biochemical pathway, known as the immune complement system. The complement component 1q (or simply C1q) is a protein complex involved in the complement system, which is part of the innate immune system. Complement activation then elicits secretion of both IL-1β and IL-18 via activation of the NLRP3 inflammasome https://pubmed.ncbi.nlm.nih.gov/23817414/ again adding to the inflammation cascade. https://forums.phoenixrising.me/thr...ed-abnormalities-in-me-cfs.90173/post-2439526

 

[Violeta]

I posted some of this once before: the reactivation of multiple herpesviruses (EBV, HHV-6) and their production of dUTPase can elicit both humoral and cellular immune responses, including the hyperactivation of Th1 and Th17 in some patients with ME/CSF which has been in the literature for awhile. It does not appear to be the cause of the problem but is instead another downstream effect if immune function is compromised, the virus compromising the immune function, or stressed and viruses are allowed to reactivate adding additional fuel to the fire of the existing problem.

That makes sense, so just continue to focus on the immune system.