Salivary DNA loads for human herpes viruses 6 and 7 are correlated with disease phenotype in ME/CFS, Lee, Lacerda, Nacul, Cliff et al, preprint 2021

John Mac

John Mac

Senior Member (Voting Rights)
Full title:
Salivary DNA loads for human herpes viruses 6 and 7 are correlated with disease phenotype in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome

Abstract
Click to expand...
Myalgic encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a complex chronic condition affecting multiple body systems, with unknown cause, unclear pathogenesis mechanisms, and fluctuating symptoms which may lead to severe debilitation. It is frequently reported to have been triggered by an infection, particularly with herpes virus family members; however, there are no clear differences in exposure to, or seroprevalence of, any herpes virus in people with ME/CFS and healthy individuals.

Herpes viruses exist in lytic and latent forms, and it is possible that ME/CFS is associated with viral reactivation, which has not been detectable previously due to insensitive testing methods. Saliva samples were collected from 30 people living with ME/CFS at monthly intervals for six months and at times when they experienced symptom exacerbation, as well as from 14 healthy control individuals. The viral DNA load of the nine human herpes viruses was determined by digital droplet PCR. Symptoms were assessed by questionnaire at each time point.

Human herpes virus (HHV) 6B, HHV-7, herpes simplex virus 1 and Epstein Barr virus were detectable within the saliva samples, with higher HHV-6B and HHV-7 viral loads detected in people with ME/CFS than in healthy controls.

Participants with ME/CFS could be broadly separated into two groups: one group displayed fluctuating patterns of herpes viruses detectable across the six months while the second group displayed more stable viral presentation.
In the first group, there was positive correlation between HHV-6B and HHV-7 viral load and symptom scores, including pain, neurocognition and autonomic dysfunction.

The results indicate that fluctuating viral load, related to herpesvirus reactivation state, may play a role in ME/CFS pathogenesis, or might be a consequence of dysregulated immune function. The sampling strategy and molecular tools developed permit large-scale epidemiological investigations.
Click to expand...

https://www.medrxiv.org/content/10.1101/2021.01.06.20248486v1
 
Last edited by a moderator:
Canadian and/or Fukuda selection criteria. Would be nice if they would give Fukuda up.

Cliff et al said:
Herpes virus reactivation might either be a cause or effect of ME/CFS manifestation: either a disturbance in immune system function caused by ME/CFS disease development enables a persistent HHV viral infection to become reactivated, or the reactivation of the virus might be the precipitating factor for the worsening of ME/CFS symptoms.
Click to expand...
Why would it necessarily be one or the other? Reduced available energy (due to ME) for the immune system might allow for herpes reactivation, which then causes issues as the immune system uses more energy trying to control it, seems to be a logical possibility to me.
 
My ME didn't start out with viral reactivations, I actually felt "virus-free" for 11 years. Something changed along the way where I'm feeling 'viral' 80% of the time. Some are actual viruses but others not so much. I'm not going to my GP every month to find out.
 
Andy said:
Why would it necessarily be one or the other? Reduced available energy (due to ME) for the immune system might allow for herpes reactivation, which then causes issues as the immune system uses more energy trying to control it, seems to be a logical possibility to me.
Click to expand...

This would be the typical progress of latent and reactivating infections. I think the authors try to clarify that the association doesn't imply causality and that HHVs are necessarily the primary target of treatment. Just because you get HSV during PEM, it doesn't mean that HSV treatment could provide any benefit. Maybe, it is a whole group of viruses that share a certain genome. The more of them you get infected with, the greater the influence on the immune system of people with certain genotypes (TBD), the greater the overall lysis/reactivation dynamic of latent co-infected virus reservoirs.

Theoretically, EBV could also play a part. Saliva samples don't indicate if lysis happens locally and contained in the lymphatic system. I think long-term studies with children could clarify which viruses initially trigger CFS, to narrow down potential commonalities and genomes. HHVs, EBV, and CMV are all known to dysregulate immune function in the long term.

I don't know any antiviral that works with the whole range of viruses. But maybe there is an antiviral that is specific to their common genomes. Regardless, virustatics might only suppress the lysis, which might influence PEM susceptibility, but altered lymphocytes would not return to their normal state because of this. This means virustatics would have to be taken continuously. The overall outcome might be similar to what has been observed for treatment-resistant Lyme Borreliosis, which is also dependant on the human HLA genotype. Initially, antibiotic therapy can help for Lyme Borreliosis, but long-term outcomes of therapy are not promising. It might work, but there are also anecdotes of it becoming worse. Maybe (true) antibiotic resistances are involved then, I don't know. The HLA type predisposes patients by general susceptibility, not antibiotic-specifically (10.1006/jaut.2000.0495).
 
So they're just replicating citation 36.

They reference citation 36 as "herpesvirus are found in saliva in CFS patients"

But it's more than that: "Human herpesvirus 6 and 7 are biomarkers for fatigue, which distinguish between physiological fatigue and pathological fatigue."

Why wouldn't sicker patients have a higher viral load? That's uniform throughout almost every illness, dermatomyositis, MS, Stevens Johnson syndrome, asthma, obstructive sleep apnea, depression.

What's your hypothesis? Why are you doing the study?
 
Only glanced at this but it reminds me of Bupesh Prusty's hypothesis i.e. ME is related to the effects of latent herpesvirus.

Extract from paper:
"The results indicate that fluctuating viral load, related to herpesvirus reactivation state, may play a role in ME/CFS pathogenesis, or might be a consequence of dysregulated immune function. The sampling strategy and molecular tools developed permit large-scale epidemiological investigations."
 
I wonder if this is the study I was going to be a participant in. I fitted most of the criteria when they were recruiting in 2015 but it turned out I wasn't eligible because I take anti-virals (acyclovir) which obviously would skew the results. I find the anti-virals help although I've been on them for so long now I don't know what would happen if I came off.
 
Figure 3 in their paper shows that concentration of the Herpes virus DNA was highest for HHV-7, than HSV-1, EBV and HHV6B.

"To investigate viral persistence, the proportion of samples from each participant that were HHV-positive over the time course was determined (Figure 3B). HHV-7 was consistently detected in all samples from the majority of participants throughout the 6 months (median for all 3 groups = 100%), whereas, HSV-1, EBV, and HHV-6B were only intermittently detected. HHV-6B was detected significantly more frequently in the ME/CFS_SA participants (median: 33.3%, IQR: 16.7–75%), than in HC (median: 8.33%, IQR: 0–41.7%; p = 0.049), but not in ME/CFS_MM participants (median: 22.5%, IQR: 0–70.8%; p = 0.28). In contrast, there was no significant difference in the frequency of detection of EBV or HSV-1 in HC compared to people with ME/CFS (Figure 3B)."
 
You must log in or register to reply here.
Back
Top Bottom