XMRV and Culturing, HERV's and more

[flybro]

Thanks Cort, that is exactly what I am thinking, what serendipity this could be for us if they really found HERV activation with the antibody, culture, antigen and EM studies. They ARE finding something and finding HERV fits well with their virachip study and the new MS research showing HERV activation. I guess we will have to wait to find out.

Does this mean........ that this could be a CFS biomarker.

Is there treatment availble for this if you can proof we have it.

XMRV is totally terrifying but it did fit with my Nans Atypical MS, my and one daughters CFSness, and my younger daughters ASD/Fragile-X symptoms. Plus where they have been finding the XMRV in animal studies seemd to add-up for CFS.

I am assuming HERV is not a dangerous as XMRV, which would make less neurotic about my children and grandchildren having a retro-virus like AIDS.

Am I wrong to hope for the HERV thing being right, rather than XMRV.

Can HERV solve the problem the way XMRV seemd to be likely to.


Thanks and sorry if I got things wrong.

 

[starryeyes]

I think we're all a bit desperate to have something solid for CFS research to get going on, and XMRV looked like it was going to be it - I don't think we can expect a forum like this to be truly balanced on this subject.

It's great to have Kurt providing a different viewpoint here - especially because it may not be what we want to hear.

Until there's independent replication of the WPI's work, we should see their Science paper as just pointing future research in an interesting direction. Hopefully it will result in something significant, but I think our hunger for some solid science is leading a lot of us to believe This Is It! The key hase been found!

The lack of positive news from alternative sources has calmed my initial excitement, but I'm still hopeful the WPI's work will lead on to something. Emotionally, it's going to be a pretty heavy blow if it doesn't - but we should still try to stay ready for that possibility.

Kurt wrote: I do respect what you say about lab experience, there is no substitute. In my case there is no substitute for knowing the back-room part of the research cycle. I known how research studies can be subconsciously biased, sometimes for political or business reasons. So I know how important a full group of studies is before reaching global conclusions, particularly about something like a retrovirus causing CFS.

Keep in mind, the WPI has never stated that XMRV causes ME/CFS.

Good question Flybro. I look forward to hearing the answer.

 

[kurt]

Does this mean........ that this could be a CFS biomarker.
Is there treatment availble for this if you can proof we have it.
XMRV is totally terrifying but it did fit with my Nans Atypical MS, my and one daughters CFSness, and my younger daughters ASD/Fragile-X symptoms. Plus where they have been finding the XMRV in animal studies seemd to add-up for CFS.
I am assuming HERV is not a dangerous as XMRV, which would make less neurotic about my children and grandchildren having a retro-virus like AIDS.
Am I wrong to hope for the HERV thing being right, rather than XMRV.
Can HERV solve the problem the way XMRV seemd to be likely to.
Thanks and sorry if I got things wrong.

First of all, this is all speculation, but based on a lot of current findings in HERV and MS and now CFS studies. I don't know if there really is a connection with the WPI study, but it seems possible to me and also other researchers I have spoken with. Anyway, if the WPI antibody studies are finding 98% and that is HERV activation, then it would seem to be a strong biomarker. But one problem with a HERV explanation is that the research is not very far along, not as far as for HIV/HTLV type infections. But evidence is mounting for HERV involvement in MS and maybe a few other diseases like CFS. If that is what WPI is finding it is a very, very big connection to make for us. Also, the HERV itself would not be contagious at all, that virus can not replicate, only be activated from our own DNA. However its triggers might be contagious in some cases, if someone is predisposed to HHV activation and you share an active herpes infection with them (which can be airborne, so maybe consistent with outbreaks). The interesting part of the HERV finding would be that there IS a causal model that is simple and obvious. For example, HERV K18 produces a super antigen (SAg), which creates a major cytokine response, with the resulting depletions like seen in CFS. And HERV W is also interesting and a little consistent with some CFS pathologies. Also, low glutathione and HHV reactivation may be triggers, and so treatment could be indirect, such as to lower HHV levels and raise glutathione (fix methylation cycle problems, etc.), so the HERVs would stop expressing. And maybe certain treatments would be found to stop the already activated HERVs. I find it interesting that at the same time this information is coming to us we have a few related treatment studies, showing positive outcomes (HHV antivirals and methylation/glutathione support). I also hope this is the answer, or something like this, it just makes so much sense and treatment is probable.

 

[starryeyes]

That's very interesting and hopeful Kurt. Thanks for explaining about HERVs.

 

[natasa778]

Kurt, I've only had time to skim through your WPI/XMRV sceptical posts, but are you trying to say that their PCR testing gives false positives, and so since they licenced the test to lombardi's lab everybody who has tested positive so far through private tests is actually a false positive?? both PCR and culture positives?

Also what about prostate cancer in vitro studies? would the virus they are finding there actually be a HERV? they are all getting false positives through PCR? there is no XMRV?

or there is only XMRV in prostate cancer, not in WPI/VIPdx tests??

 

[Funkster]

XMRV = ME, HERV = CFS - are you both right?

Kurt and Gerwyn,

Why not consider that you both are right;

Lets assume that ME and CFS is overlapping, but not identical diseases. There are overweight of some symptoms in ME and others in CFS.

ME is caused by an Exogenous Retroviruses named XMRV - http://en.wikipedia.org/wiki/Xmrv

CFS is caused by an Endogenous Retrovirus named HERV - http://en.wikipedia.org/wiki/Endogenous_retrovirus

Outbreaks would be HERV - hence there was a CFS-outbreak in Incline Village etc.

Single patient could be HERV or XMRV - depends on spesific symptoms and biomarkers.

RNAse L cleavage would in this scenario be a linkage to patients with XMRV and therefore a biomarker (remember that was Mikovits first clue and Silverman is still working on this in prostata cancer (http://www.youtube.com/watch?v=RWOWvdiXiSE).

It is not totally unliky that you can have CFS as a result of a HERV.

My bias and situation (been sick for appr. 1 year):
I have no active viruses (HHV, EBV, CMV, HPV etc) - all negative
I have no bugs (borrelia, bartonella, coxiella, rickettsia) - all negative
I have some enterococcos and streptococcos in the gut and a bit low on e.coli - running on antibiotics and probiotics as well as B12 shots, 5-HTP and some other supps starting today, including a cfgf diet.

The most essential test results from Red Labs in Belgium;

CYTH
IL-2/IL-4, ratio TH1/TH2, result 857 (reference 2,00 - 100,00)
IFNg/IL-4, ratioTH1/TH2, result 162 (reference 10,00 - 350,00)

ANOX, Total antixoidant capacity, result 0,76 (reference 0,33 - 0,65 nM)
C4AS, C4 A Serum level, result 1744 (reference 20,00 - 1400,00 ng/ml)
CD57, CD57 Absolute count, result 54 (reference 60,00 - 360,00 cells/ul)
ELAS, Elastase expression, result 850 (reference 0,00 - 150,00)
PERF, Perforin mRNA expression, result 837 (reference 250,00 - 750,00)
RNAE, RNase L cleavage assay, result 1,2 (reference 0,00 - 0,50)
sCD14, Soluble CD14, result 6521 (reference 2800,00 - 5000,00 ng/ml)

IMPH
CD16CD56+, NK cells CD3-CD16CD56+, result 7 (reference 1,90 - 19,60 %)
CD3+, T cells CD3+, result 75 (reference 62,00 - 84,40 %)
CD3+CD4+, T cells CD3+CD4+, result 43 (reference 29,00 - 67,10 %)
CD3+CD8+, T cells CD3+CD8+, result 29 (reference 10,50 - 44,30 %)
CD4/CD8, ratio T cells CD4/CD8, result 1,48 (reference 0,72 - 2,89)

The doctor says;

You have a general immune activation. We can see that you have an intracellular infection, most likely from a virus, but we cant find any of the usual viruses. You have several of the "biomarkers" that we find in many ME patients, but you are a "clean case" and have been ill for a short period. Your NK cells are still working pretty well.

My bet is that I have ME casued by XMRV.

I have a 20 year old son that came down EBV in March 2008 - still sick. Gradually getting more and more fatigued, low puls (42 resting puls), freezing, but less cognitive problems than me.

My bet is that he has CFS - and maybe a HERV rather than XMRV.

I have a 5 year old son - showing signs of mild autism/asperger. He has stomach trouble, night sweats, emotional outbursts, cognitive problems, reduced eye contact, varying degree of symptoms in different periods.

My bet is that he has ME - childrens edition caused by XMRV, vertically transmitted.

All three share some genetic predisposition for this.

Comments and critics appreciated?

- Funkster

PS! Still waiting for my XMRV Serology Test Result to come back from Red Labs, Belgium.

 

[starryeyes]

Thanks for the update Funkster. It's so heartbreaking to hear of kids with illnesses like this.


tee

 

[natasa778]

Sounds good Funkster, my first issue with that hypothesis is that XMRV would easily reactivate HERVs, so you would have both.

Also, just as with XMRV, whatever else is capable of reactivating HERVs would most likely be pathogenic in itself, so although HERV activity could be a biomarker for CFS/autism/MS whatever, it may not prove to be that useful at the end of the day.

btw your son sounds exactly like mine nowdays (used to be much much worse)

 

[Gerwyn]

Gerwyn,
I/O psych - see http://en.wikipedia.org/wiki/Industrial_and_organizational_psychology

Systems science - see http://en.wikipedia.org/wiki/Systems_science

My post-doc at the mil research lab was as a research psychologist. I assume you know research teams often pull in allied professionals, I was in an experimental psych lab that was working on advanced training problems. So that was my post, not my credential, sorry if that was not clear. I am a systems scientist in the technical sense, but work cross-discipline so wear many hats. My job was as a research psychologist. I was well qualified for my work, ran several large-scale studies, published, etc. I have also taught ed. psychology at graduate level so they must have thought my background qualified...

Expertise is one of my 'topics', and I have used cognitive task analysis and designed training systems using that method. An example of my work, I meet with experts, could be doctors, lawyers, engineers, business experts, educators, whatever. Then work through various protocols to elicit expert performance models from them. What I do with the models varies by project, in the medical case I helped analyze how Cardiologists read EKG for purposes of training GPs to do a better job at that. So I worked with the subject-matter experts. Sometimes I help clients produce new training technologies, sometimes just produce new performance models or guidelines, or help solve professional performance problems. You might say I am a type of facilitator, certainly not the expert, but I have to learn everything in the expert process I am analyzing.

So given that pre-CFS background I have a kind of mindset to analyze things, including what is happening now with XMRV but also the larger picture of research into CFS.

And I do respect what you say about lab experience, there is no substitute. In my case there is no substitute for knowing the back-room part of the research cycle. I known how research studies can be subconsciously biased, sometimes for political or business reasons. So I know how important a full group of studies is before reaching global conclusions, particularly about something like a retrovirus causing CFS.

so you worked with systems and processes

No in my experience there there is no substitute for lab experience and backroom knowledge of the research proceess from a scientific and a political perspective.

 

[Gerwyn]

Kurt and Gerwyn,

Why not consider that you both are right;

Lets assume that ME and CFS is overlapping, but not identical diseases. There are overweight of some symptoms in ME and others in CFS.

ME is caused by an Exogenous Retroviruses named XMRV - http://en.wikipedia.org/wiki/Xmrv

CFS is caused by an Endogenous Retrovirus named HERV - http://en.wikipedia.org/wiki/Endogenous_retrovirus

Outbreaks would be HERV - hence there was a CFS-outbreak in Incline Village etc.

Single patient could be HERV or XMRV - depends on spesific symptoms and biomarkers.

RNAse L cleavage would in this scenario be a linkage to patients with XMRV and therefore a biomarker (remember that was Mikovits first clue and Silverman is still working on this in prostata cancer (http://www.youtube.com/watch?v=RWOWvdiXiSE).

It is not totally unliky that you can have CFS as a result of a HERV.

My bias and situation (been sick for appr. 1 year):
I have no active viruses (HHV, EBV, CMV, HPV etc) - all negative
I have no bugs (borrelia, bartonella, coxiella, rickettsia) - all negative
I have some enterococcos and streptococcos in the gut and a bit low on e.coli - running on antibiotics and probiotics as well as B12 shots, 5-HTP and some other supps starting today, including a cfgf diet.

The most essential test results from Red Labs in Belgium;

CYTH
IL-2/IL-4, ratio TH1/TH2, result 857 (reference 2,00 - 100,00)
IFNg/IL-4, ratioTH1/TH2, result 162 (reference 10,00 - 350,00)

ANOX, Total antixoidant capacity, result 0,76 (reference 0,33 - 0,65 nM)
C4AS, C4 A Serum level, result 1744 (reference 20,00 - 1400,00 ng/ml)
CD57, CD57 Absolute count, result 54 (reference 60,00 - 360,00 cells/ul)
ELAS, Elastase expression, result 850 (reference 0,00 - 150,00)
PERF, Perforin mRNA expression, result 837 (reference 250,00 - 750,00)
RNAE, RNase L cleavage assay, result 1,2 (reference 0,00 - 0,50)
sCD14, Soluble CD14, result 6521 (reference 2800,00 - 5000,00 ng/ml)

IMPH
CD16CD56+, NK cells CD3-CD16CD56+, result 7 (reference 1,90 - 19,60 %)
CD3+, T cells CD3+, result 75 (reference 62,00 - 84,40 %)
CD3+CD4+, T cells CD3+CD4+, result 43 (reference 29,00 - 67,10 %)
CD3+CD8+, T cells CD3+CD8+, result 29 (reference 10,50 - 44,30 %)
CD4/CD8, ratio T cells CD4/CD8, result 1,48 (reference 0,72 - 2,89)

The doctor says;

You have a general immune activation. We can see that you have an intracellular infection, most likely from a virus, but we cant find any of the usual viruses. You have several of the "biomarkers" that we find in many ME patients, but you are a "clean case" and have been ill for a short period. Your NK cells are still working pretty well.

My bet is that I have ME casued by XMRV.

I have a 20 year old son that came down EBV in March 2008 - still sick. Gradually getting more and more fatigued, low puls (42 resting puls), freezing, but less cognitive problems than me.

My bet is that he has CFS - and maybe a HERV rather than XMRV.

I have a 5 year old son - showing signs of mild autism/asperger. He has stomach trouble, night sweats, emotional outbursts, cognitive problems, reduced eye contact, varying degree of symptoms in different periods.

My bet is that he has ME - childrens edition caused by XMRV, vertically transmitted.

All three share some genetic predisposition for this.

Comments and critics appreciated?

- Funkster

PS! Still waiting for my XMRV Serology Test Result to come back from Red Labs, Belgium.

Hervs are neither replicative or infective, would not enter cells during the transfective process or be then available for harvesting---What ever they found was an active virus capapble of replication and thus not a herv.Herves would not cause outbreaks like the one you mention but could be activated by the presence of an infective ageant of some kind

 

[Gerwyn]

Hervs are hervs they cannot infect other cells >they can be made to bud in artificial conditions but never do in real life that is why they are classified as HERVS!! The genetic sequence of the virus corresponded to XMRV as independently typed by the workers who first discovered and characterised the genotype of XMRV.

Mulv type gammaretrovirus is not a cleassification of any Herv

The WPI tests were indeed complicated and precise --this is why a lay person cant hope to evaluate them objectively .

If lack of robustness and accuracy are the issue the european studies have cornered the market

 

[Gerwyn]

I receive inputs from other labs (and also individuals). That is how I learn how retrovirologists outside the WPI circle interpret the XMRV tests. This has been educational and I am trying to pass along what I am learning. This is not rumor, but information sharing about issues to look at regarding risk factors in testing for XMRV.

None of the information I have mentioned about: HERV cross-reaction with MuLV; problems with many prior research efforts to find retroviral explanation for diseases; issues regarding whether or not culture was performed before PCR; or issues of systems biology and models for CFS are rumors. Those are all factual discussions based on what I have learned from outside experts via back-channel. If you want more information, just look up some of the references I have given. There is no 'context' for this, other than the fact that I am talking to researcher scientists with experience in the research and testing world who are looking at the WHOLE body of evidence and not just hunting down the information that supports their personal viewpoint.

As for the XMRV studies themselves, they are out there, many more than I know about personally, and in time I expect we will hear report after report.

what on earth has systems biology got do do with the issue

What you have learned from outside experts is hersay

The point is to look at the whole body of evidence presented in the WPI study and not the bits you find convenient.

The Genetic sequencing of MUlv and XMRV reveal huge differences in deletion downstream of the alternative start codon

I dont know what you are trying to say with your herv recombination theory

 

[natasa778]

Hervs are neither replicative or infective, would not enter cells during the transfective process or be then available for harvesting

Gerwyn, it HAS been speculated in the past by virologists that something like this MIGHT be in the realm of possibilities (also what about recombination of hervs with exogenous elements etc) but something like this would be such a major discovery that it would have major far reaching implications for all of medicine not to mention virology... and would take the science team straight to Oslo for a massive Nobel Prize, that kind of discovery.

My problem with this is what about prostate cancer studies, are they all looking into a 'fake xmrv'? Are those poor monkeys at Yerkes not really full of replicating xmrv, it just was put into them and then disappeared, and what those scientists are seeing in their tissue samples are reactived HERVs? Kurt?

As someone said is XMRV a figment of their collective imagination? Or are they all right but it is just WPI and VIPdx who are halucinating?

 

[natasa778]

Antibodies to XMRV

btw Kurt one of the recent CROI presentations, by Abbotts lab guy, was solely devoted to their developing XMRV-specific antibodies. They used them to detect xmrv in the blood of healthy blood donors...

 

[Knackered]

As for the XMRV studies themselves, they are out there, many more than I know about personally, and in time I expect we will hear report after report.

Have you been tested for XMRV?

Would you share with us the results?

 

[Funkster]

Gerwyn

1a) I fully accept that WPI found XMRV in some patients - can you confirm that they cultured the cells before they did run the PCR, or did they not?
1b) What about all those patients that test negative, still claiming they have CFS - will they all test positive on the antibody test - hence more than 95 % of all patients have XMRV?
2) Can you rule out that a reactived HERV could cause some or all of the symptoms in a CFS patient (e.g. mitochondrial dysfunction, low blood volum, OI)?
3) Can you rule out that the Incline Village was an outbreak of an infective agent e.g. HHV6 or EBV (not XMRV), and that HERV was activated as a result of that agent in some patients?
4) Can you rule out that ME and CFS is two different diseases caused by two different retroviruses?

If, yes to all of the above - I rest my case .

- Funkster

 

[Gerwyn]

Gerwyn, it HAS been speculated in the past by virologists that something like this MIGHT be in the realm of possibilities (also what about recombination of hervs with exogenous elements etc) but something like this would be such a major discovery that it would have major far reaching implications for all of medicine not to mention virology... and would take the science team straight to Oslo for a massive Nobel Prize, that kind of discovery.

My problem with this is what about prostate cancer studies, are they all looking into a 'fake xmrv'? Are those poor monkeys at Yerkes not really full of replicating xmrv, it just was put into them and then disappeared, and what those scientists are seeing in their tissue samples are reactived HERVs? Kurt?

As someone said is XMRV a figment of their collective imagination? Or are they all right but it is just WPI and VIPdx who are halucinating?

recominations can sometimes take place this is one of the mechanisms involved in zoonosis but this kind of recomination would require neuclotide changes never before witnessed.

 

[jspotila]

Cautionary Note

Have you been tested for XMRV?

Would you share with us the results?

Given that this forum can be read by anyone (and has been cited in several news articles), I suggest that individuals make their own decisions about whether to share any kind of medical information. A willingness, or lack thereof, to share private medical information should not become some kind of test of a poster's veracity or anything else. I'm not saying that Knackered intended the question as a litmus test, just waving a caution flag against our going in that direction.

Anyone can read our posts, friends. Let's respect each other's rights to keep medical information private.

 

[Gerwyn]

Gerwyn

1a) I fully accept that WPI found XMRV in some patients - can you confirm that they cultured the cells before they did run the PCR, or did they not?
1b) What about all those patients that test negative, still claiming they have CFS - will they all test positive on the antibody test - hence more than 95 % of all patients have XMRV?
2) Can you rule out that a reactived HERV could cause some or all of the symptoms in a CFS patient (e.g. mitochondrial dysfunction, low blood volum, OI)?
3) Can you rule out that the Incline Village was an outbreak of an infective agent e.g. HHV6 or EBV (not XMRV), and that HERV was activated as a result of that agent in some patients?
4) Can you rule out that ME and CFS is two different diseases caused by two different retroviruses?

If, yes to all of the above - I rest my case .

no they concentrated their sample activated and the did pcr they were samples of fresh peripheral blood

it is likely but by no means certain it is a dustbin diagnosis some may have toxicity or other factors causing mito damage

what would cause the reactivation there are too many systems involved to be a herve causing it

the indian village outbrake could have a number of causes. what ever did it must have had the ability to severely affect many systems in a very short space of time not a herve possibly several but unlikely. most common cause of multiple herve activation is a retrovirus as they are part of the intrinsic defence sysytem.Just because Hervs are expressed that does not mean they cause harm.They are key elements built into our genome to fight off other retroviruses.this is sometimes called the genomic immune system.Hervs are responsible for a great many of our epigenetic responses as they act to regulate the expression of genes--gene switches if you like.Now if something was to insert within Herv DNA at different sites then there would be mayhem.The symptoms are nowhere near the same as those caused by the other two viruses

only as part of a prolonged autoimmune response and then not directy causative

No I cant rule out that ME and CFS are different diseases i think they are.As for CFS it is an entirely social construct dreamed up my psychos and has no objective relationship to the illness it tries(not very hard) to describe.I think the causative agent is XMRV but In ME the systems affected are more widespread

you cant rule anything out in science as the answers are always couched in terms of probability and closest approximation of truth we have bearing in mind the weight of evidence.At the moment XMRV as the causative agent is the most parsimonious explanatory hypothesis If cfs has any meaning as a diagnosis at all.

 

[Cort]

Gerwyn please respond to the fact that WPI researchers apparently did not culture their samples before PCR testing yet now Dr. Mikovits states that culturing is absolutely necessary. This is how this got started - as a way to explain this oddity. Do you agree that there is no evidence in the paper that the PCR samples were cultured first?

If not then please give us some idea of why culturing would be necessary later on?

I would note that this could be the reason Dr. Vernon came down so hard on the WPI for not telling us more about those original patients. She noted that first they didn't need to culture and then they did - that could suggest that those patients were different; that they were much sicker and thus the virus was much easier to find. That is one interpretation is it not?