Herpesvirus 6 & 7 as biomarkers to distinguish between physiological and pathological fatigue

[MikeJackmin]

Full Title: Human herpesvirus 6 and 7 are biomarkers for fatigue, which distinguish between physiological fatigue and pathological fatigue.

Biochem Biophys Res Commun. 2016 Jul 7. pii: S0006-291X(16)31125-1. doi: 10.1016/j.bbrc.2016.07.010. [Epub ahead of print]
Aoki R1, Kobayashi N2, Suzuki G3, Kuratsune H4, Shimada K2, Oka N2, Takahashi M2, Yamadera W5, Iwashita M5, Tokuno S6, Nibuya M7, Tanichi M7, Mukai Y8, Mitani K9, Kondo K2, Ito H5, Nakayama K5.

Abstract
Fatigue reduces productivity and is a risk factor for lifestyle diseases and mental disorders. Everyone experiences physiological fatigue and recovers with rest. Pathological fatigue, however, greatly reduces quality of life and requires therapeutic interventions. It is therefore necessary to distinguish between the two but there has been no biomarker for this. We report on the measurement of salivary human herpesvirus (HHV-) 6 and HHV-7 as biomarkers for quantifying physiological fatigue. They increased with military training and work and rapidly decreased with rest. Our results suggested that macrophage activation and differentiation were necessary for virus reactivation. However, HHV-6 and HHV-7 did not increase in obstructive sleep apnea syndrome (OSAS), chronic fatigue syndrome (CFS) and major depressive disorder (MDD), which are thought to cause pathological fatigue. Thus, HHV-6 and HHV-7 would be useful biomarkers for distinguishing between physiological and pathological fatigue. Our findings suggest a fundamentally new approach to evaluating fatigue and preventing fatigue-related diseases.

http://www.ncbi.nlm.nih.gov/pubmed/27396623

 

[JaimeS]

Am I reading that right? They figure because HHV-6 and 7 don't increase in CFS, CFS is physiological fatigue?

 

[MikeJackmin]

Am I reading that right? They figure because HHV-6 and 7 don't increase in CFS, CFS is physiological fatigue?

I understood it to mean that the biomarkers could distinguish between physiologic fatigue - normal fatigue, that resolves with rest - and pathological fatigue, which is abnormal and not resolved by rest.

 

[roller]

Our results suggested that macrophage activation and differentiation were necessary for virus reactivation.

However, HHV-6 and HHV-7 did not increase in obstructive sleep apnea syndrome (OSAS), chronic fatigue syndrome (CFS) and major depressive disorder (MDD), which are thought to cause pathological fatigue.

why would "macrophage activation and differentiation" be defective in ppl with CFS ?

 

[MikeJackmin]

why would "macrophage activation and differentiation" be defective in ppl with CFS ?

Just guessing, but perhaps this activation is something that is normally triggered by the regular cycle of exercise - fatigue - rest - recovery. Those with pathological fatigue have fatigue that exists outside of this cycle, which is caused by other things, so it might make sense that the biomarkers would differ.

 

[JaimeS]

Def macrophages have been shown to be 'off' in ME patients multiple times. Try pubmed

 

[Bob]

Am I reading that right? They figure because HHV-6 and 7 don't increase in CFS, CFS is physiological fatigue?

I think they are saying that HHV-6 and 7 increase in ordinary (physiological) fatigue but do not increase in the pathological fatigue seen in CFS and other illnesses. They say that HHV-6 and 7 may be useful markers to help distinguish physiological fatigue from pathological fatigue. I'm not quite certain what the benefit would be; surely patients know whether they have pathological fatigue or not?

 

[halcyon]

They say that HHV-6 and 7 may be useful markers to help distinguish physiological fatigue from pathological fatigue.

I'd hazard a guess that they aren't useful given the mixed evidence in this area. There seems to be numerous studies that have found increased HHV6 and/or 7 DNA in CFS patients, though most of these studies were looking at WBCs and not in saliva like this study.

 

[Hip]

They say that HHV-6 and 7 may be useful markers to help distinguish physiological fatigue from pathological fatigue. I'm not quite certain what the benefit would be; surely patients know whether they have pathological fatigue or not?

I think they are claiming that the lack of increase in HHV-6 and HHV-7 DNA in the saliva after exercise in ME/CFS patients could be used as a sort of biomarker for ME/CFS, although it is not unique to ME/CFS, as this lack of increase is also found in obstructive sleep apnea and major depressive disorder.

 

[sarah darwins]

Can anyone give a brief, plain English description of why HHV 6 and 7 DNA levels in saliva might be expected to increase after exertion in a healthy person?

 

[msf]

Can anyone give a brief, plain English description of why HHV 6 and 7 DNA levels in saliva might be expected to increase after exertion in a healthy person?

Because the exertion was of a sexual nature?

 

[Hip]

Can anyone give a brief, plain English description of why HHV 6 and 7 DNA levels in saliva might be expected to increase after exertion in a healthy person?

In the full paper, the authors speculate that in healthy people, HHV-6 and HHV-7 increase in the saliva after exercise by the following mechanism:

• HHV-6 and HHV-7 lie dormant (as a latent infection) in macrophages in the spleen.

• In murine testing, they found exercise induces the inflammatory cytokine IL-1β in the spleen.

• This increase in IL-1β in the spleen causes macrophage activation and differentiation.

• This in turn causes reactivation of HHV-6 and HHV-7 inside the macrophages.

• That then results in elevated levels of these viruses in the saliva.


Then the authors seem to suggest (but I am not really clear why) that in ME/CFS, obstructive sleep apnea and major depression, this increase in IL-1β after exercise does not occur, and that's why you don't get the HHV-6 and HHV-7 reactivation after exercise in these conditions.

 

[sarah darwins]

In the full paper, the authors speculate that in healthy people, HHV-6 and HHV-7 increase in the saliva after exercise by the following mechanism:

• HHV-6 and HHV-7 lie dormant (as a latent infection) in macrophages in the spleen.

• In murine testing, they found exercise induces the inflammatory cytokine IL-1β in the spleen.

• This increase in IL-1β in the spleen causes macrophage activation and differentiation.

• This in turn causes reactivation of HHV-6 and HHV-7 inside the macrophages.

• That then results in elevated levels of these viruses in the saliva.


Then the authors seem to suggest (but I am not really clear why) that in ME/CFS, obstructive sleep apnea and major depression, this increase in IL-1β after exercise does not occur, and that's why you don't get the HHV-6 and HHV-7 reactivation after exercise in these conditions.

Thanks, Hip. I can sort of follow that. So now they need to explain why the increase in IL-1β after exercise does not occur in certain conditions, yes? Although the fact that they're suggesting it happens in major depression as well seems to make this less promising as a line for biomarkers.

 

[Hip]

Before anything like this can become a biomarker, I think you would have to validate it against hundreds of diseases, to make sure your biomarker only appears in your target disease, and not in others (like say lupus, hepatitis C, hypothyroidism, anemia, etc).