Schmitt K, Richter C, Backes C, Meese E, Ruprecht K, Mayer J.
Human endogenous retroviruses of the HERV-W group comprise hundreds of loci in the human genome. Deregulated HERV-W expression and HERV-W locus ERVWE1 encoded Syncytin-1 protein have been implicated in the pathogenesis of multiple sclerosis (MS). However, actual transcription of HERV-W loci in the MS context has not been comprehensively analyzed so far. We investigated transcription of HERV-W in MS brain lesions and white matter brain tissue from healthy controls by employing next generation amplicon sequencing of HERV-W env specific RT-PCR products, thus revealing transcribed HERV-W loci and relative transcript levels of those loci. We identified greater than 100 HERV-W loci to be transcribed in human brain, with a limited number of loci being predominantly transcribed. Importantly, relative transcript levels of HERV-W loci were very similar between MS and healthy brain tissue samples, refuting deregulated transcription of HERV-W env in MS brain lesions, including the high-level transcribed ERVWE1 locus encoding Syncytin-1. Quantitative RT-PCR likewise did not reveal differences in MS when regarding HERV-W env general transcript or ERVWE1 and ERVWE2 specific transcript levels. Yet, we obtained evidence for inter individual differences in HERV-W transcript levels. Reporter gene assays indicated promoter activity of many HERV-W LTRs including structurally incomplete LTRs. Our comprehensive analysis of HERV-W transcription in human brain thus provides important information on the biology of HERV-W in MS lesions and normal human brain, implications for study design, as well as mechanisms by which HERV-W may (not) be involved in MS.
The history of virus work in MS has been the consistency of the inconsistency and not virus implicated in MS has found universal support. This is no different here.
Prof G Down under has been arguing for the role of human endogenous retroviruses in the pathogenesis of MS. These are viruses that have incorporated themselves into our genome. About 8% of our genome may be of viral origin. In some studies it has been argued that these, usually dormant viruses become active and could be a trigger of MS. This may be a dual viral hit such as with EBV. However this study did not find evidence for this. The level of virus (HERV) replication was no different between MSers and non-MSers and puts a chink in the armour of the Charcot Project. However were these samples from active MS….Well most post-mortem samples are from secondary progressive MS and not early active MS, which is where the Prof Gs are aiming.
The Prof Gs have put the drugs companies money where there mouth is and got off their bums to try and test an idea. It may be a wrong idea, hopefully the trial design is good and large enough.
If the approach succeeds it is a game changer, requiring a rethink for many.
Some of You have chastised Team G for not reporting this paper as some form of conspiracy. We do the blog when we have time, which is not all the time and may not have have internet access 24/7.
We are not reporters…If we were we would be making up silly titles and talking about a cure every second word, as we saw last week in some of the rags called Newspapers. So Hedgehog takes a few here, otherwise sme of you (trolls) would get a monthful!.
Do we write about everything to do with the published Literature? …..NO
We simply do not have the time…or the energy and we tend not to post on review articles. Their are loads of MRI papers for example, Maybe is one of our MRIers wants to blog you will get more.
Are we a source of News…..MAYBE
Prof G keeps an eye out but we are not in the business of promoting companies stocks when they annonunce a new trial that is ten years away from becoming an MS drug. We are interested in the results of the studies. Some stories are released from press embargo before the source information comes out…these tend not to be covered until the source information is availble.
Do we cherry pick the stories we report?…..OF COURSE WE DO.
There is not enough time in the day to report every thing and we are not the worlds paper reviewers. However we try to select things that are of topical and may be of interest to people with MS. We may post things relevant for our students/team. We are not Pharma sponsored! Sometimes it may take too long to explain something and we don’t have the time to do it justice.
Do the subjects covered focus around our research interests?….YES DEFINATELY
Part of our remit is public engagement in science about our research. To do this we need to provide sufficient knowledge and the background such that you can understand our work. This may mean posting of subjects outside the scope of some papers that hit the news. Some of you may not find them interesting others may, but it makes us different.
Do the themes follow your thoughts?…YES OF COURSE THEY DO
Look at the conflicts of interests statements to decide it you wish to be sceptical. If you want alternative opinions look elsewhere also.
We do not post on things that do not fit with our research Ideas…..NO..NOT ON PURPOSE
If topical and relevant they are presented. ProfG does not believe in the same things I may believe in for example, defense of your argument is part of the scientific process.