ERVs and Multiple Sclerosis, #3

ERVs and Multiple Sclerosis

ERVs and Multiple Sclerosis, #2

Hmmm... This new paper on the association between 'active' ERVs and Multiple Sclerosis is a step back, and a step forward, at the same time:

Expression of HERV-Fc1, a human endogenous retrovirus, is increased in patients with active Multiple Sclerosis.

If you go back and read ERVs and MS #2, youll see that we have an endogenous retroviral protein, gag, expressed in elevated levels in the brains of MS patients. The gag is from the HERV-W family of ERVs, related to syncytin.

In this paper, however, they associated Multiple Sclerosis with an increase in a HERV-H, HERV-Fc1, RNA (and to a degree, protein), in serum and blood cells.

There are some problems with this.

HERV-Hs have lots of mutations. Stop codons, frame shifts, etc. While HERV-Fc1 is on the X chromosome, which might help to explain why more women get MS than men, just because RNA is made, that doesnt mean any protein is being created from that RNA. And though they looked for protein in this paper, really, the 'best' test they had was looking for HERV-Fc1 RNA. If they wanted me to believe their flow data looking for HERV-H protein, I need to see a histogram, not a column graph 'summarizing' their flow data. Sorry. Technically, I want to see an immunoprecipitation so I can SEE the protein, but whatever.

Furthermore, they looked for alterations in gene expression in PBMC. While this might have an impact on the altered immune systems of MS patients, which might have a hand in the pathology of MS, without direct evidence of the connections between HERV-Fc1, a particular immune response and disease, this is just a hypothesis, not a conclusion. What is going on in MS patients brains?

The more logical conclusion that I am drawing from this papers data is that in MS patients, there is a body-wide alteration in epigenetic profiles that is effecting everything from brains to blood cells, leading to the expression of ERV RNA, which sometimes is capable of being translated into ERV proteins, which may or may not be actively contributing to disease. Which we already kinda knew...

Does that mean I think this paper is crap?

No.

HERV-W being expressed in the brains of MS patients doesnt do us a hellofalot of good. How would you detect that in routine screenings/diagnostic screenings for MS? Brain biopsies? Uh, no. And what are we supposed to do about it once we detect it? What if the damage is already done? What good is this information to us, clinically?

But maybe HERV-Fc1 RNA is upregulated in PBMC very early in MS disease. It is relatively trivial to draw blood from someone to test for HERV-Fc1 RNA. Maybe HERV-Fc1 is an easy diagnostic marker.

Maybe we can find HERV-Fc1 RNA long before the symptoms of MS start to appear.

Maybe we can use epigenetic modifying drugs to correct the future-MS-patients epigenetic profiles before whatever is going wrong, goes wrong enough to cause disease. Again, it would be relatively trivial to monitor how well treatments are working-- look for HERV-Fc1 RNA in blood draws.

So I think this paper is step back, in terms of what has been done before along this avenue of research (ERVs and MS). It looks like the HERV-W papers from 2009. But it is also potentially a big step forward for the diagnostic/disease monitoring of Multiple Sclerosis. We will see!