Multiple sclerosis: Discovery of a mechanism responsible for chronic inflammation

[keepontruckin]

https://www.sciencedaily.com/releases/2019/05/190510091354.htm

 

[Hope4]

@keepontruckin Thanks very much for posting this.

Unfortunately, the full text is pay-per-view.

Here is a link to the journal abstract:

http://emboj.embopress.org/content/early/2019/05/08/embj.2018101107

The Abstract:

Abstract
Several autoimmune diseases including multiple sclerosis (MS) cause increased transcription of endogenous retroviruses (HERVs) normally repressed by heterochromatin. In parallel, HERV‐derived sequences were reported to drive gene expression. Here, we have examined a possible link between promoter and enhancer divergent transcription and the production of HERV transcripts. We find that HERV‐derived sequences are in general counter‐selected at regulatory regions, a counter‐selection that is strongest in brain tissues while very moderate in stem cells. By exposing T cells to the pesticide dieldrin, we further found that a series of HERV‐driven enhancers otherwise active only at stem cell stages can be reactivated by stress. This in part relies on peptidylarginine deiminase activity, possibly participating in the reawakening of silenced enhancers. Likewise, usage of HERV‐driven enhancers was increased in myelin‐reactive T cells from patients with MS, correlating with activation of nearby genes at several sites. Altogether, we propose that HERV‐driven enhancers constitute a reservoir of auxiliary enhancers transiently induced by stress while chronically active in diseases like MS.

... [chart]

Human endogenous retroviruses (HERVs) derived from ancient exogenous viruses can act as cis‐enhancers. This study shows that increased disease‐related gene expression is in part due to a chronic increase of HERV cis‐enhancer activity in the context of autoimmune diseases.

• Enhancers driven by HERVs are enriched in the neighborhood of immune genes.
• HERV‐driven enhancers are mostly active in embryonic cells but silenced in mature adult tissues.
• Extensive stress causes transient reactivation of HERVtranscription.
• In multiple sclerosis, some HERV‐driven regulatory regions become chronically active.

 

[Rufous McKinney]

By exposing T cells to the pesticide dieldrin, we further found that a series of HERV‐driven enhancers otherwise active only at stem cell stages can be reactivated by stress.

Wish I could translate that into: something I could grasp. (hah). I am struggling to figure out why I got so much MORE sick quite abruptly 10 months ago. I went from: just lousy to: I see myself heading to permanent bedridden.

I think something alive reactivated. I got two SEVERE norovirus-like horrific nausea events,three months apart, and even went to the ER the second time. Something about those two events: is supposed to tell me something about: WHAT THE HECK is actually going on here.

And I think its some type of reactivation because: well frankly I was so isolated at both times I wasn't around new germs. And eating the same food, not food poisoned.

 

[junkcrap50]

EBV can re-activate HERVs.

 

[Richard_HERVk]

I got infected HERV-K by a kiss at end of January 2020. I tried Metagenome Sequencing for find pathogen this April as I was sick seriously. I found I infected HERV unexpectedly when I got the result of sequencing.

I think this virus is transmitted and I have my Metagenome Sequencing data of 2018 and 2019 can prove it. At those times I got infected by parasites and fungus but hospital can not find out what I infected so I tried sequencing to help myself to diagnostic and got successful results.

Gene sequencing is really useful for diagnostic.