HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome. Rodrigues et al. 2019

[John Mac]

Abstract
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFSMS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases.

Here the expression of Endogenous retroviruses K and W (HERVK and HERVW) was determined in blood from moderately and severely affected ME/CFS patients. HERVK was overexpressed only in moderately affected individuals and HERVW showed no difference. This is the first report about HERVK differential expression in moderate ME/CFS.

https://www.biorxiv.org/content/10.1101/693465v1?rss=1

 

[InitialConditions]

I mean wow.... can't even get the acronym right: 'CFSMS' (!), 'CFS/ME' and 'ME/CFS' in the abstract alone. That's one way to put readers off.

 

[Lucibee]

Looks like this research is using some of the LSHTM CureME biobank samples.

I've found some other articles that may put it into context wrt ME/CFS.

One of the reasons for looking at this is that HIV seems to induce expression of HERV-K, particularly during active infection: https://retrovirology.biomedcentral.com/articles/10.1186/1742-4690-9-6
"Increased HERV expression is often seen during carcinogenesis and in autoimmune diseases such as multiple sclerosis [2], but it is unclear whether the increased expression is a cause or consequence of the disease."

ref 2 is this paper: Kurth, Bannert. Beneficial and detrimental effects of human endogenous retroviruses https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.24902

 

[Mithriel]

Why would HERVK be overexpressed in the moderately affected but not the severely affected? It just seems strange.

 

[Dolphin]

T

I mean wow.... can't even get the acronym right: 'CFSMS' (!), 'CFS/ME' and 'ME/CFS' in the abstract alone. That's one way to put readers off.

True, though this is only at preprint stage. Hopefully most of such errors particularly in the abstract should go after it goes through peer review and editing.

 

[Hoopoe]

Why would HERVK be overexpressed in the moderately affected but not the severely affected? It just seems strange.

It seems to be a null result but the authors are trying to avoid that conclusion. This difference is just reaching the p=0.05 threshold. On other parameters the patients don't differ from controls.

 

[Lucibee]

Why would HERVK be overexpressed in the moderately affected but not the severely affected? It just seems strange.

I guess we'll have to wait for the whole paper, but my guess is that if HERV-K expression requires the presence of active viral replication from another agent (eg HIV), you might only see that in moderately affected patients because of the energy demands it places on cellular mechanisms.

 

[Snow Leopard]

Why would HERVK be overexpressed in the moderately affected but not the severely affected? It just seems strange.

Indeed. It could suggest that "moderate" and "severely" are two different diseases. Or that the results are null...

 

[wigglethemouse]

Don't know who this guy is but he posted a snapshot re: RCCX and HERV-K. Looks like he is based in Seattle, Washington from his profile

 

[rvallee]

Don't know who this guy is but he posted a snapshot re: RCCX and HERV-K. Looks like he is based in Seattle, Washington from his profile

Uh. Interesting!

His Twitter bio:

Genome-centric #biotech #nerd #genetics#MECFS #Researcher and #biohacker for extremely complex diseases. I help doctors make progress in their most tough cases

I can't wait until the people who want to tackle the toughest challenges understand this is one of the most interesting ones. So much potential to discover entire new areas of medicine. There's definitely a Nobel prize somewhere in the pipeline once we crack this egg.

 

[wigglethemouse]

Uh. Interesting!

His Twitter bio:

Kris Fobes offered more info on his work in 7 replies in the same Twitter thread as above.

1. I haven't seen this paper yet, but I have seen similar! The problem that I find with most studies is that we are trying to find markers that fit across the majority of ME/CFS cases. I strongly believe that this is why we are failing to make better progress in treatments.

2. If we look at HERV-K specifically in this scenario, the HERV-K transcription is inside the gene "C4a/b" as one of its introns. Our population is split, some of us carry a C4 short gene which excludes HERV-K and some of us carry a C4 long gene which includes HERV-K

3. C4 genes are heavily expressed during immune response and inflammation and plays a major role in our complement cascades. So the question here really comes down to the chicken or the egg.

4. If someone has constant immune response and C4 "Long" genes then increased HERV-K transcription could just be a sign of high immune response and inflammation but not necessarily a CAUSE of the immune response and inflammation.

5. If someone had C4 "Short" genes than increased HERV-K transcription would be much more interesting since the HERV-K transcription would not be coming from our standard C4 gene expression.

6. Thats why this kind of genetic testing is so important. In the image, we can see that 3 of the samples have C4 "short" genes by the loss of the HERV-K transcripts in the C4 genes. Those samples might have super severe #MECFS but might not have the increased HERV levels.

7. On the flip side, someone with C4 "Long" genes and a completely different disease the increases C4 activity could also have increased HERV-K activity. Extremely personalized treatment approaches are the only way we are going to find the true underlying drivers of #MECFS

Just to add, isn't it cool that S4Me posts many interesting papers

 

[Andy]

Background
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/MS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases.

Methods
Here the expression of Endogenous retroviruses K and W (HERV-K and HERV-W) was determined in blood from moderately and severely affected ME/CFS patients through real time PCR.

Results
HERV-K was overexpressed only in moderately affected individuals but HERV-W showed no difference.

Conclusions
This is the first report about HERV-K differential expression in moderate ME/CFS. Although the relationship between HERVs and ME/CFS has yet to be proven, the observation of this phenomenon deserves further attention.

Open access, https://autoimmunhighlights.biomedcentral.com/articles/10.1186/s13317-019-0122-8