German study finds xmrv

[free at last]

Hey Free,

I didn't mean to discount your experience or ideas. I have done the same thing, messed with diet, vitamins, etc. Who knows what they will discover, but it would be nice if it were simple, even if it's scary-simple.

This study doesn't give us what we need, but it does effectively put us back to the first day after the Science paper came out by showing that the negative studies were rubbish. Even if there are other factors, at least we have the hope that if we can take care of the XMRV we can all jog and smoke pot again (I prefer a nice glass of wine). I did not mean to sound dismissive - just wanted to point out that, as I understand it, XMRV could be the whole answer for many of us. Take good care.

Bluebell No i didnt take it like that at all, first you made me laugh, the knife in the head at the docs, those pesky eggs again or is it sauages. second it really made me think yes i do this, and look for clues out of frustration, as im sure so many do, also out of sheer frustration. when infact your so right, just the chance that xmrv is the culprit is enough by itself isnt it. No more looking under the bed for demons that may not exist there, just because you know there is a killer in the house somewhere

My greatest fear is of course that im not xmrv positive, and be right back where i started 15 years ago. All those years looking for bad eggs. I came to a point that i just gave up ever beliveing i would find a cause for all the fear frustration and illness. That this horrible thing called ME/CFS does to each and everyone of us. How messed up in the head can someone be, to actually want to have a retrovirus rather than more years of uncertainty and a great big ZERO.

I dont want to go to my grave never ever knowing why my life was so destroyed. The chance for a conclusion and understanding ( not sure if i will have treatment or not yet ? those drugs seem so toxic too) and a regaining of power and self respect to all those who laugh at us, and belittle us, when they havent got a damm clue how truely teffifying this illness can truley be. well 2 fingers up at them you know Bluebell.

im still in a state of shock to think our time might just be coming this time around,no more false dawns surely. im scared to have this virus but im even more scared not to have it.how nuts is that. At least if i go downhill again, i can fight back this time. So many are not with us now the brave souls who have fallen. Sophia and Lynn would have been a honour to have known them
And to Sharpe Wessley and White they have no idea what they have done,even if they think there right, for all these reasons please make it true this time. The suffereing and ridicule must end

 

[Mark]

Originally Posted by Gerwyn
because XMRV does its damage when inserted which is different to HIV and inserts into start sites of genes.it moves around the genome.If it inserts into a regulatory gene which regualtes 40 other genes then some consequences are virtually inevitable

That would cause chaos.

You talked about inserting in start sites before. It is still not clear to me. Can you explain it again?

Do I get this right, that if XMRV writes itself over a 'start site' (one which contains genes that regulate or activate maybe 40 other genes - epigenetics?) you will get many more immune regulation and other problems and a much more serious condition? And is it also likely that the (last count I heard) 6 strains of XMRV discovered so far may prefer to bind to different sites? Could the nature and location of the genetic damage also be related to co-factors lowering the immune resistance? Viruses, immuno-suppressant drugs, prolonged stress, persistent exposure to environmental toxins such as toxic mold, perhaps drink and drugs, all these might help open the door for XMRV?

Going back to basics, and just in case it's either wrong or helpful to somebody: my understanding is that retroviruses use reverse transcription (RNA-to-DNA conversion) to overwrite their DNA over the DNA of infected cells. There will be various target sites on various cells that are suitable for them to bind to, and those will define different behaviour as specific aspects of the natural genetics are disrupted.

This all seems well related to the existing body of research and to recent results: Dr Kerr, as I understand it, recently identified 80 genetic sequences which are abnormal in ME/CFS patients, and it could be that these are somehow related to the corruption of DNA by XMRV? (Not sure how that might work). Also, one of my own doctors, citing Dr Myhill's theoretical model, mentioned to me some years ago that just such DNA corruption (which Biolab were then seeking evidence for in 'DNA adducts' tests) was believed to be at the base of the chain of events that led to enzyme production deficiencies causing failures of digestion and consequent highly specific vitamin deficiencies and sutble damage to specific parts of the immune system.

That whole theory sounds to me ever-increasingly plausible these days, as an explanation for at least some of the problems of ME,CFS,MCS,MU and WTF patients...

One final highly speculative idea: would respiratory infection be consistent with infection via XMRV-infected/ mediated air pollution such as ye olde (and new) toxic mold? Another possible route of infection? This and other plausible co-factorial explanations of the Royal Free Outbreak might be an interesting topic to revive one day soon?...

 

[Forbin]

Forgive me if Im misremembering this, but I recall reading/hearing/seeing somewhere that, even if a retrovirus does nothing once it is inserted into the cells DNA, its mere presence may still cause changes to the surface of the cell which might then be recognized by the immune system. Could that lead to a chronic activation of the immune system and could that chronic activation alone be causing many of the symptoms experienced as CFS?

 

[anciendaze]

...or maybe i'm reading too much in. maybe it's too simple to assume one little virus could be responsible for so much. but i do gotta wonder???
what did i maybe get that was passed down thru my genes?

This is still very early days in the XMRV business. We don't know many emotionally significant things for sure. I've had to come to terms with similar issues of my own.

This is not simply a matter of getting something in your genes. There are other kinds of "vertical transmission". You can get a viral infection that crosses the placenta, or a virus expressed in mother's milk, while your newborn immune system is not yet fully competent. Retroviruses add the possibility of genes inserted in germline cells as well as ordinary somatic cells. Vulnerability to infection can be inherited through ordinary genetics of the immune system. These genes are regularly reshuffled inside the body so the immune system can generate antibodies to novel pathogens never seen by any ancestor.

Right now, it begins to look like there have been far more people exposed to XMRV than have developed CFS/ME. Many seem to show no ill effects whatsoever. We don't know why some do and others do not.

You have to think about this in the way you might think about knowing the winning lottery number. If you had only known that number, you could have millions of dollars, and you could have given those you love many things you have not. Does that make you feel guilty? It seems ridiculous.

 

[justinreilly]

off-topic

My dad went to boarding school there. If you could see the way he loads a dishwasher you would understand;-)

Ha! My roommate bought a Bosch dishwasher a month ago. The instruction book is bigger than the book for my car. It has pages of diagrams about where to load which utensils!

 

[justinreilly]

The sad part is it would be very hard for worker's compensation board to accept this kind of exposure- they want a source- in order to explain infection and insure this was not caught outside of work. Interestingly, should firefighters get throat or lung cancer, they get compensated, regardless whether they smoke- and WCB will never ask them to prove from which house they got the exposure from...

You should be recompensed w/o question, obviously.

In the Bible (Osler's Web) an early large survey in the US found that 90% of "CFS" patients were working in only one of five jobs at onset: doctors, nurses, flight attendants, pilots and teachers. 'nuff said.

My overall take on ME transmission is XMRV and probably one or more other Retroviruses, probably including DeFreitas retrovirus widely spread by air, but only a minority of people exposed contract ME (because of genetics including RNAse L defect and others per Kerr). ok, we can all go home now. Well, I guess not quite, but this study is great as everyone is saying.

I do love that this was published in a CDC journal!

The whole fraud is going to come crashing down on the charlatans, perhaps soon. To mix/ switch metaphors: we got to just keep pushing; don't give up; this boulder we've been pushing for decades is almost over the cliff. The momentum is building!:victory:

 

[justinreilly]

XMRV doesn't exist in the UK according to Wessely & McClure - they say. ''If it was there, we would have found it''. And the other classic: "We are confident that our results show there is no link between XMRV and chronic fatigue syndrome, at least in the UK. Egg on face much for the Imperial College London I think. I wonder how stupid they will look in the next few months!!!! Did they realliy think no one else would bother looking at XMRV? :victory:

Their extreme arrogance and outlandish statements are finally really going to get the best of them! They have proved you can pretty much say whatever anti-scientific BS you want to re: ME because next to noone cares about us or ME enough to question them or learn about this disease.

But they erred hugely by saying they were "1000% sure" that XMRV did not exist in the UK because they would have found it (and chastising Lombardi et al. for publishing their supposedly sloppy study!!)!

Also the fact that BMJ closed ranks and collectively threw out there all the misinformation on ME & XMRV they could is going to expose that there actually is a conspiracy, if only in a loosely knit, wink, wink kind of way; but a conspiracy against ME science and ME patients nonetheless.

 

[alex3619]

Total Prevalence of XMRV

Hi, I have been commenting on this but am probably not the only one. The 3.7% figure is for healthy people. As we discover more and more diseases that are implicated it will rise. It is also affected by the percentage of people with these diseases who are xmrv positive - but this figure goes up and down as we learn more. As a result the real prevalence of xmrv is the healthy plus the sick. Six percent is one possibility, but if you were to claim 4.5% or 9% you could still be right. One thing seems clear, the general trend is up, and the last time I calculated it I came to 5.1%, but had to leave out many diseases because I had no good prevalence data. Bye, Alex

I did read on here somewhere that overall global prevalence was ~6%. It was in an email someone posted.

 

[alex3619]

Hi omerbasket, Judy Mikovits reports that two thirds of family members of xmrv positive patients in the original study are also xmrv positive. She also reports that these people have seriously high prevalence of cancers and autism. Bye, Alex

When the Science study was published, Dr. Coffin wrote an article titled: "New virus, How many old diseases?" (or something like that...). As I think of it, I think XMRV might be the cause for many diseases, including ME/CFS, prostate cancer, other cancers (perhaps lymphoma and/or leukemia), fibromyalgia, autism, gulf war syndrome, MS or at least some cases of MS and who knows what (in the following diseases, XMRV was found in different numbers of cohorts in studies: ME/CFS, prostate cancer, fibromyalgia, autism and some atypical cases of MS - so it might not be just my imagination).

Another thing I think about: I think a very good study to see the infectivity of XMRV would be to take people who are XMRV positive and to test their families for XMRV. Now, if you want to see if XMRV is transsmisble in every-day's-activity - meaning via saliva, urine, sweat etc., you would probably want to test families in which you know that one of the children have XMRV (but you didn't already test anyone else from that family), and that is because you don't want to focus on cases were there is a reasonable chance that XMRV have been transsmited during sex that the child was born with XMRV. I think that would be an interesting kind of study, a pretty easy one to make (relatively) and that would be able to tell us a lot of things quickly, before approaching to the scientific experiments that might be harder to do and that the conclusions from them might be more difficult.

 

[parvofighter]

The plot thickens: the Germans are learning from their XMRV mistakes

@eric_s made a comment waaay back @ post #202 (http://www.forums.aboutmecfs.org/showthread.php?5031-German-study-finds-xmrv/page21) that got me thinking. And the synapses finally connected:

Now it seems we have two German studies, one positive and one negative (Bannert). I think in both studies there were researchers involved from the RKI (Robert Koch Institut). Is there any paper available about the Bannert study?

What i'm thinking is this:
If those two studies have used different methods to try to find XMRV (i know one looked in blood and the other one in other substances, but i mean the PCR or whatever they've used), then it will probably only be a matter of time until the Bannert group repeats their study, this time using the more successful method.
This will be very interesting because it will more or less prove if the XMRV/CFS association is true or not. Now that there is another team in another part of the world that actually knows how to find XMRV, if they confirm the Science study's findings, then it will be clear enough, i think.

Does anyone know if the Bannert group could not find any XMRV at all? Or did they find the ~3% that would have to be there? If they couldn't find any, i think it's pretty safe to assume that they have used a different method compared to this latest study or did not work properly. On the other hand it seems a bit strange that people from the same institute work on studies parallely and don't exchange information about how to do it correctly. I'm really interested to see results of a study done at the RKI in PWCFS, using the techniques of this study, because i think the RKI is a good adress.

I REALLY REALLY hope you're right about this eric. I did a little digging on those German studies, and was intrigued to see one name associated from the Robert Koch Institute, with all 3 of the German studies:

Prof. Dr. Oliver Hohn co-authored these 3 German papers:

• The Bannert paper: actually Dr Hohn is the lead author on this paper: Lack of evidence for xenotropic murine leukemia virus-related virus(XMRV) in German prostate cancer patients. (http://www.ncbi.nlm.nih.gov/pubmed/19835577?dopt=Abstract&holding=f1000,f1000m,isrctn). Remember their Conclusion?

CONCLUSION: Our results indicate a much lower prevalence (or even complete absence) of XMRV in prostate tumor patients in Germany. One possible reason for this could be a geographically restricted incidence of XMRV infections.
​

Well, we can now strike a geographically restricted incidence off the list - at least for Germany. I don't have access to the full paper, but the abstract makes no mention of XMRV prevalence in controls. Anyone have the full paper, so we might follow up on eric's question?
​

• Presentation at the Centennial Retrovirus Meeting of the Institute of Molecular Genetics in Prague: Mechanisms of Disease: Prevalence of XMRV in Prostate Cancer and Chronic Fatigue Syndrome Patients in Germany. (http://www.crm2010.org/list-of-posters.html) As I recall, this was a "negative" paper. I had asked Dr Hohn to email me a copy of the paper if possible, but haven't heard back. Anyone have access to this paper/poster??
  

• This latest one: Xenotropic Murine Leukemia Virus-related Gammaretrovirus in Respiratory Tract ( http://www.cdc.gov/eid/content/16/6/pdfs/10-0066.pdf)
  

Now as I recall from Dr Mikovits' ProHealth talk, Dr Bannert was working with Dr Singh (and Mikovits too, I seem to recall) to recalibrate their testing methods. Remember that the initial Bannert study had already been submitted for publication, when the Science paper came out. It may well be that these Germans are leading the pack in scientific rigor and nimbleness. A couple of false starts. Identify the defect in testing methods. Learn from international best practices. Take the field by storm.

At least that's what I hope they're doing... and there are many indications this is the case.

Will Hohn's teams retest their previously "negative" prostate/ME/CFS samples?
I wrote another email to Dr Hohn, asking if he could clarify whether they would be retesting samples from their earlier negative prostate cancer and ME/CFS work? If he replies, I'll ask him for permission to repost, and if he does give me permission, I'll follow up with you guys.

Bottom line, at least some researchers in the world are voraciously devouring any opportunity to research this XMRV beast in a variety of contexts. AND being sufficiently humble and flexible to recognize that there may be more than one way to arrive at robust answers, and that their own methods may need a major overhaul. The Japanese have a maxim that goes something like: "Fall down six times, get up seven". And that's exactly what the Germans are doing. Good stuff, eh?

A far cry from the single-celled organisms that are valiantly trying to suppress the advancement of knowledge on XMRV. I love it.

 

[JT1024]

Parvo....go for it! We know you can hunt!

Glad to see you back in the online and in the hunt! Wish I could be more active and help!

Keep up the good work..

 

[Nina]

Now as I recall from Dr Mikovits' ProHealth talk, Dr Bannert was working with Dr Singh (and Mikovits too, I seem to recall) to recalibrate their testing methods. Remember that the initial Bannert study had already been submitted for publication, when the Science paper came out. It may well be that these Germans are leading the pack in scientific rigor and nimbleness. A couple of false starts. Identify the defect in testing methods. Learn from international best practices. Take the field by storm.

At least that's what I hope they're doing... and there are many indications this is the case.

Will Hohn's teams retest their previously "negative" prostate/ME/CFS samples?

Unfortunately, I am not exactly sure this is what's happening. On Nov 30, the Charit announced on their site that they had been looking for XMRV in CFS patients and found it was "rare". After that, Bannert's team went back to their labs to retest their samples, stating they would work closely with the Americans now. According to Dr. Judy, they have received reagents and protocols in early January. She hasn't heard from them ever since. Next thing we know, Bannert's team present their findings at the Prague conference and say they still haven't found XMRV in CFS patients.

I hope you are right and Hohn will now proceed to retest Bannert's samples, but right now nothing indicates he does.

 

[CBS]

Prof. Dr. Oliver Hohn co-authored these 3 German papers:

• The Bannert paper: actually Dr Hohn is the lead author on this paper: Lack of evidence for xenotropic murine leukemia virus-related virus(XMRV) in German prostate cancer patients. (http://www.ncbi.nlm.nih.gov/pubmed/19835577?dopt=Abstract&holding=f1000,f1000m,isrctn). Remember their Conclusion?

CONCLUSION: Our results indicate a much lower prevalence (or even complete absence) of XMRV in prostate tumor patients in Germany. One possible reason for this could be a geographically restricted incidence of XMRV infections.
​

Well, we can now strike a geographically restricted incidence off the list - at least for Germany. I don't have access to the full paper, but the abstract makes no mention of XMRV prevalence in controls. Anyone have the full paper, so we might follow up on eric's question?​

Here's the link to the full paper: http://www.retrovirology.com/content/6/1/92

 

[parvofighter]

Dissent in the ranks?

I hope you are right and Hohn will now proceed to retest Bannert's samples, but right now nothing indicates he does.

I hope so too, Nina! Thanks for the update, and I hope that we'll hear more soon. It is an interesting situation though, isn't it? If Bannert and Hohn are NOT on the same page, I wonder how that might affect future research @ Robert Koch on XMRV? Is Hohn sufficiently independent (and does he have independent funding) to be able to forge ahead, and redo his work with Bannert et al? Given that Hohn was the lead author of the "Bannert paper", hopefully he'll have the clout to have his way....

Anyone have an inside scoop?

 

[parvofighter]

"5 healthy control individuals" used in Bannert/Hohn study

Thanks CBS!

Eric had asked the following:

Does anyone know if the Bannert group could not find any XMRV at all? Or did they find the ~3% that would have to be there? If they couldn't find any, i think it's pretty safe to assume that they have used a different method compared to this latest study or did not work properly.
​

OK eric, here's what I found from the Bannert/Hohn paper provided by CBS:

Xenotropic Murine Leukemia Virusrelated Gammaretrovirus in Respiratory Tract In total, 146 sera from prostate cancer patients and 5 healthy control individuals were tested negative for antibodies binding recombinant XMRV gp70 and Gag proteins in ELISA, although postive control immunized mouse sera reacted strongly (Fig. 5A and 5B). One patient serum that reacted strongly in ELISA against the recombinant pr65 protein was subsequently tested by immunofluorescence assay using HEK 293T cells expressing XMRV and cells expressing the gp70- or pr65 proteins alone. No XMRV specific binding was seen, indicating a non-specific ELISA reaction.

As additional controls we tested the cell lines 22Rv1 (XMRV positive [17]) and DU145 (XMRV negative [9]). As expected, 22Rv1 was found to be strongly positive for RNA transcripts and for provirus (with In-For/Deletion-Rev primers), while DU145 was negative in both PCR approaches (data not shown).

From Figure 2: Nested-PCR screen of the first 16 QQ patients (lane 1-16) with the In-For and Deletion-Rev primer pair (upper panel) and In-For and In-Rev primer setup (lower panel); lane 17 = mouse tail DNA, lane 18 = water control outer PCR mix, lane 19 = water control inner PCR mix, lane 20 = pXMRV, lane 21 = pDG75, marker = 100 bp marker.In other words, the original Hohn/Bannert paper used water as a negative control, as well as cell line DU145 (XMRV negative). And they also tested "5 healthy control individuals".

Based on these low control numbers of actual humans, it would be impossible to determine prevalence in controls for comparison.

But did Hohn/Bannert in the original negative prostate paper use the same methods as Hohn did in his positive respiratory secretions paper????

Anyone??
​

 

[Gerwyn]

She doesn't address it directly there, but instead outlines the WPI methods that include the activation/stimulation/biological amplification/culture steps.

However, she and Ruscetti state it directly in their recent response in Science magazine (bolds mine):

and of course they were not CFS patients in the first place.Cfs does not exist in any objective sense.It is merely a diagnosis driven by definition.Change the diagnosis and you change the nature of the cohort

 

[Countrygirl]

Is bone marrow not one of the places the WPI isolated XMRV. Bone marrow might need to be screened as well. I don't carry a donor card. I wonder if immunosupressant drugs might actually slow XMRV replication.

Mithriel[/QUOTE]

Hi Mithriel,

Just to add that I received an e-mail from Dr Judy saying that they have discovered XMRV in bone marrow and she would like more samples. I hoping that one is going to be sent soon from the UK to her.

Warmest regards,

C.G.

 

[Gerwyn]

That would cause chaos.

You talked about inserting in start sites before. It is still not clear to me. Can you explain it again?

I will try Lans,

All genes have sequences of DNA called start codons. this is the point that dna transcriptase binds to and begins to transcribe the proteins that the gene codes for which may or may not regulate the activity of other genes.XMRV and the other gamma retroviruses bind preferentially into start codons.This may change the reding frame of the codon leading to the gene in question been left on or turned off.Some genes inhibit body processes some enhance.Just for good measure xmrv binding overlaps the start codons and the gene proper leading to insertional mutagenesis and polymorphisms in the proteins produced! As you say chaos

 

[natasa778]

I just did a quick statistical analysis. I combined the subjects into two groups; those that had received a transplant in one group, and everyone else in another group. The p-value of the XMRV prevalence between them was 0.02, meaning that the higher prevalence in the transplant recipient group is statistically significant and unlikely to be due to random chance. Then I cut XMRV prevalance in the transplant group in half, to represent the idea that half of them were infected upon receiving their transplants. The p-value was then 0.53, which is not statistically significant. So the hypothesis I posted above is consistent with the statistical data from the study.

But remember that they received transplant tissue or organs from healthy donors, so their chance of getting contaminated organs would have been around 3%.... meaning that would not account for 9% prevalence.

I still feel a more likely explanation that it was a long-standing xmrv infection in the first place that might have contributed to their organ failure, or them needing marrow transplant for whatever reason.

 

[natasa778]

Could the nature and location of the genetic damage also be related to co-factors lowering the immune resistance?

Yes. But apart from messing up with gene expression related to immune resistance, remember the recent discovery of how SU proteins (surface unit proteins, used for attachment/entry into cells) 'confuse' and lower immune response in the host. I wonder if those would be expressed by xmrv even in the latent state...

Ops, sorry Mark I just reread and realised I probably misunderstood your question. Do you mean to ask whether immune-lowering factors could in some way influence site of insertion or activity of inserted provirus?