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XMRV Study No. 4

Discussion in 'XMRV Research and Replication Studies' started by Orla, Feb 25, 2010.

  1. Esther12

    Esther12 Senior Member

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    Maybe XMRV is just a common factor which contributes to CFS? Making recovery more difficult, lowering tolerance for the normal strain of life etc.

    I've taken these negative studies more seriously than some here, and think they add up to a really serious blow to the likelihood of an XMRV CFS connection. But I also think that some of the information coming out about XMRV makes it seem more plausable as a causal factor than I thought when I'd been assuming it was similar to HIV.
  2. kurt

    kurt Senior Member

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    I agree, there are some interesting angles for XMRV, such as the prostate studies that show neuroendocrine tissue infection, but you have to look at the whole picture, including epidemiology and the full range of signs and symptoms in CFS, and the validation efforts from outside labs to see if this really makes sense. The failure of three validation studies is serious, even given the methodological differences. There are many ways bias can influence researchers, causing them to use methods that are more likely to support their preconceived views. That can be a problem on both sides of a finding like this, so at this early stage it is difficult to know what is really happening in ANY of the labs, including WPI/VIP and the labs trying to validate the Science article finding. Over time we will know better as the drama continues and more studies emerge.
  3. Gerwyn

    Gerwyn Guest

    a retrovirus actingas an inserted psuedogene can easily cause the symptom range of cfs.The virus at low tire indicates that it spends most of its time integrated
  4. kurt

    kurt Senior Member

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    Yes, I agree this is possible in theory, if the pseudogene alters the function of some critical system in a destructive way. In fact, that might be true for any and all unexplained diseases that involve metabolic dysfunctions. If you have not read it yet I suggest looking at the 'Rumor Viruses' article, searching for retroviral explanation is almost inevitable for any disease of unknown cause today.

    Human RNA "Rumor" Viruses: the Search for Novel Human Retroviruses in Chronic Disease (.pdf) (published by the American Society for Microbiology)

    But the question is not whether this is possible, but whether this is what is actually happening. Does the evidence support this? Even a virus with low titre has to be found, and WPI says they found it by PCR and so other labs should also. WPI finds it sometimes without culturing, so should the other labs, even if it is low titre, particularly those using more sensitive PCR.

    As for a retrovirus explaining the signs and symptoms, I agree there is one retrovirus that can explain CFS, that is HERV K18, which is often activated in CFS and produces a superantigen protein, leading to cytokine problems. I have not seen a good model of how XMRV might create CFS, but there is a reasonably solid case for K18, particularly given that it can be activated by herpes reactivation, which can itself probably be triggered by a combination of genetic and external factors consistent with CFS epidemiology.

    So even if data suggests one explanation, like a retrovirus, you have to find a probable causal model, then also look at the viability of alternate explanations, then collect enough evidence to determine which explanation makes the most sense given the data. One problem we have with ME/CFS is that we are decades behind where we should be in the research/consensus model process. So we are not collectively familiar with this process, how brutal the scientific ups and downs can be (again, see the 'Rumor Viruses' article!!!). Also due to being behind, we do not have many alternate explanations to compare to the XMRV Hypothesis. I am using HERV K18 only as an example that there are and will be alternatives to XMRV. There is a flurry of activity right now in ME/CFS research and I hope we will see several more very strong alternate explanations, so we have something to compare with the XMRV hypothesis.
  5. HowToEscape?

    HowToEscape? Senior Member

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    Hm. Somehow we need to get the research world interested in this disease, not just one or another virus. Even if it turns out that XMRV lights off some or most ME cases, that doesn't get us a cure. That or some other combination of factors could set off a disease which remains *after* the trigger is removed. We've just been ignored for too long - the science is difficult and it appears that politics shut the door on mounting the scale of research needed.

    While everyone tends to feel that causes close to home are the most important, a better than average case exists for finding a cure for CFID/ME. It takes down people who were previously healthy and had 20-40 years before retirement, sometimes even teenagers. Preventing new cases and gaining back even 1/4 of us who could return to work would more than pay for a full-scale research effort.
    Compare this to the cost vs benefit of the anti-cancer effort and it clear something's not right.
  6. Gerwyn

    Gerwyn Guest

    i think we have covered the PCR issues enough times there was a world of a difference between the PCR post amplification and activation used by The WPI and failed attemps to recover the virus from whole blood.

    A hypothesis should indeed account for all the observations.so we have TGf beta1underxpression raised nitric oxide levels IFN alpha beta overespression .Glutathione depletion IL1 depletion.Abnormal T4 to T8 ratios Nk depletion T1 to t2 switching.Microgial abnormalities.I am sure that I have missed a few.Cytocines can be elevated in particular chemokine.Any hypothesis would have to account for these disparate observations.Elevated cytokines would not

    Hervs are part of the intrinsic defence system so an activated Herv is strong evidence of an assaulr by an exogenous retrovirus.
    HERVK18 can be activated by herpes and EBV in in vitro cell line experiments.

    HERVk18 has been shown to be activated by ifn alpha in vivo which is produced by any virus infection.

    A Herv has a specific locus of integration and endogenous retrovirus has many. Therefore unless the claim that any virus infection can cause ME by activating HERV K 18 this lacks the explanatory power of an endogenous retrovirus.One would also have to question why anyone who gets a virus infection doesnt get ME

    "Probably " is just speculation unless something has been observed then it cant form the basis of an explanatory scientific hypothesis
  7. natasa778

    natasa778 Senior Member

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    just curious about mito markers, are there any? lactate, aspartate aminotransferase, creatine kinase etc any markers?
  8. Gerwyn

    Gerwyn Guest

    told you i had forgot things add mito markers to list latate ATP ox phos etc
  9. natasa778

    natasa778 Senior Member

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    this is all found in HIV, I found fascinating as it completely parallels what is found in autism, I have references somewhere but summary of dysfunctions
    HIV retrovirus causes calcium overload and mitochondrial dysfunction (CFS?)
    HIV causes oxidative stress and glutathione depletion (CFS?)
    HIV causes microglial activation and inflammation (CFS?)
    HIV combined with bacterial agents causes breakdown of the blood brain barrier (CFS?)
    HIV causes glutamate exitotoxicity (dyregulated GABA/glutamate mechanisms in CFS?)
    HIV causes vasoconstriction (CFS?)
    HIV inhibits methylation...
    there is also autoimmune pathology etc... And for most of the above the virus would not even have to be actively replicating....


    other clinical findings HIV:
    Leaky gut and malabsorbtion of nutrients
    Dysregulated production of digestive enzymes (impaired pancreatic function)
    Abnormal immune reactions to gliadin and casein
    Lactose intolerance
    Sugar intolerance
    Inability to digest complex carbohydrates
    Inability to absorb fats and proteins
    Gastrointestinal pathogen overload: secondary intestinal viruses, bacterial overload.
    Bacterial translocation - LPS etc found in sera
    Abnormal immune reactivity to candida albicans.
    Impaired fine and gross motor skills in HIV positive children
    Impaired sensory – auditory and visual processing
    Subclinical hypothyroidism (in adults, no data on children)


    all of the above found in idiopathic autism, I suspect the same in CFS??



    not to say that hhv6 for example could not do all that, maybe
  10. kurt

    kurt Senior Member

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    That is interesting. Did you look also for a list of the differences between AIDS and CFS? Looking just at similarities can be misleading. Also, without knowing the % of the AIDS patients that have each of these symptoms this list is pretty meaningless. For example, if some of these are only found in a small % of AIDS patients they might be unrelated to the central pathology, ordinary secondary problems.

    Also, which of these does the HIV virus itself cause? Many of those items are common in chronic herpes reactivation, particularly hhv6. And if other factors can cause hhv6 activity then all this shows is the power of herpes in an immune-compromised individual.

    I believe severe fatigue unrelieved by rest and PEM are unusual outside ME/CFS. Retroviral AIDS and Autism may share some problems with us but they do not create ME/CFS. Clearly something else is happening in our case.
  11. Gerwyn

    Gerwyn Guest

    HIV tat causes direct mitochondral damage reducing ability to fotm ATP hence causing post exhertional malaise.

    Looking for differences can also mislead ,.perhaps you would list symptoms of ME not found in aids.

    These symptoms dont occur in chronic herpes reactivation.

    HHV 6 encephalitis could cause some of the symptoms but there is no sign of encephalitis in ME.

    Herpes is of course a family of viruses

    .Most HHv6 infections are asymptomatic and the link with the virus and other. symptoms has not yet been determined.

    There is some in vitro work that HHv6 may potentiate the effect of the aids virus.

    I find your comment re the power of herpes in immunocompromised individual puzzling.

    It is the HIV that initially causes the damage to the immune system this will inevitably cause the reactivation of a latent virus your argument appears somewhat tautological
  12. natasa778

    natasa778 Senior Member

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    The first half of the list is mainly in vitro studies, so yes it would be solely down to HIV and not any co-infections.

    The second part is moslty clinical findings in HIV+ people. No, I didn't calculate statistics for each finding... And yes of course impossible to know if real life whether it would be HIV or other infections causing all those things in HIV+ individuals, but that is not an argument AGAINST retroviral involvement in CFS, if anything it would be a pro argument. Especially in the light of recent findings of XMRV Env proteins blocking the immune defences, potentially opening the door for other infections to establish permanence, an AIDS-like scenario is quite likely.

    It would be good to see if HSV6 or any other virus can cause all that, at least the first half (in vitro ones) of the things on the list - do you have info?

    Didn't dr Klimas comment on how her HIV patients nowdays are doing well and are healthy, and her CFS patients are very poorly.

    There could be something specific to XMRV (or a similar non-HIV retrovirus, did you see the rabbit retrovirus link to Sjogren's I posted?) that blocks ATP production that leads to fatigue specific to ME. Or some retroviral mechanism that interferes with ryanodine receptors On the other hand it is somewhat pointless arguing about what is causing the fatigue, and how, as we do not know WHAT the main mechanism is that must go wrong for fatigue to develop (or do we?)
  13. natasa778

    natasa778 Senior Member

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    but HHV6 is causing fatigue wouldn't HIV positive be the first place for HSV6 to make home and cause fatigue. If immunosupression means opening the door to HHV6, and if HHV6 is what causes the fatigue, then most of HIV+ would probably be having CFS symptoms.

    btw as far as autism not sharing chronic fatigue that is impossible to answer with a yes/no, for many reasons 1. Energy metabolism is different in children so if same thing that causes CFS is present in a 3 year old child it may not cause/manifest as severe fatigue 2. I suspect many kids with autism could well be chronically tired but would not able to describe it! Also don’t forget that in children generally fatigue can lead to hyperactivity and/or irritability etc all sorts of ‘behaviours’ could well be at least in part down to feeling crap
  14. kurt

    kurt Senior Member

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    Here are some of the symptoms of HIV from About.com and the Mayo Clinic. Again, you have to look at both similarities and differences to compare with ME/CFS.

    Common HIV Infection Symptoms:

    Purple lesions on the skin
    Rapid weight loss
    Night sweats and fever
    White spots on the mouth, tongue, or throat
    Pneumonia
    Fever
    Headache
    Sore throat
    Rash
    Fatigue (not CFS type, just CF)

    Swollen lymph nodes — often one of the first signs of HIV infection
    Diarrhea
    Cough and shortness of breath
    The development of an opportunistic infection — an infection that occurs when your immune system is impaired — such as Pneumocystis carinii pneumonia (PCP)
    A CD4 lymphocyte count of 200 or less — a normal count ranges from 800 to 1,200
    Soaking night sweats

    Shaking chills or fever higher than 100 F (38 C) for several weeks
    Dry cough and shortness of breath
    Chronic diarrhea
    Persistent white spots or unusual lesions on your tongue or in your mouth
    Blurred and distorted vision
    Weight loss
    Soaking night sweats
    Swelling of lymph nodes for more than three months
    Chronic diarrhea
    Persistent headaches

    And in some cases there are NO SYMPTOMS AT ALL.

    Is there cross-over with ME/CFS? Probably. But I suspect you could also find a nice list of similarities between ME/CFS and MS, Cancer, Heart Disease, Hepatitis, Chronic Mono/EBV, ciguatera poisoning, Lyme Disease (almost identical, BTW), mold illness, EMF sensitivity, and about 100 other conditions. I doubt the cross-over between AIDS and CFS requires retroviral infection.
  15. kurt

    kurt Senior Member

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    Good points. After studying the methylation hypothesis for CFS (which I think may be very close to the truth, but maybe not the whole story) I have seriously wondered if CFS is simply an adult-onset subset of autism, there is a lot of evidence to support that in the pathology. In which case we could indeed have something AIDS-like, but caused by pathological gene expression due to various trigger events/toxin loads/infections and a number of unfortunate SNPs in various immune, detox and adrenal/stress management systems. So instead of retroviral cause maybe genetic cause with various triggers including herpes reactivation?
  16. cfs since 1998

    cfs since 1998 *****

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    And in most cases of XMRV there are NO SYMPTOMS AT ALL. So WHAT IS YOUR POINT.

    And why the heck did you list the same symptoms 3 times?
  17. natasa778

    natasa778 Senior Member

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    that is a bit of an oxymoron because a retrovirus can easily be a trigger.

    Also 'genetic cause' term is almost completely meaningless in this context! Is lung cancer in smokers of a 'genetic cause'?

    consider this: about 30-50% of HIV+ kids develop symptoms of autism, to various degrees. One of the main determinants (if not THE main determinants) seems to be a certain SNP in CCR5 chemokine receptors - some CCR5 snp's are protective, some expose membrane to Env toxic effects (through messing up membran calcium signalling and CREB down the line...)

    So would you say that HIV-induced CCR5-gene-determined neurological dysfunction has a 'genetic cause'?
  18. kurt

    kurt Senior Member

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    Most cases of XMRV? Last I checked, XMRV was a hypothesis with no proven causal model and at this time no proof it is anything but a passenger virus. I was not trying to make a point, except to show some of the symptoms of AIDS, judge for yourself if that looks like CFS to you. And I did not notice listing a symptom 3 times, that was just three lists put together, as I said in my post, from About.com and Mayo Clinic. What I am trying to address is the level of speculation here that ME/CFS equals XMRV, which not even WPI is saying at this point.

    'Genetic cause' is not meaningless here, but may not have been the best term, probably would be better to say genetic predisposition. But when a gene expression becomes pathological that can certainly be a cause for disease. As for the HIV+ kids that develop a type of autism, you are making my point indirectly. No, I would not say the HIV in that case had a genetic cause, but the autism certainly could have viral triggered genetic cause, or at least the genes appear to be a necessary co-factor.

    So are you saying you don't believe ME/CFS could have genetic involvement? I am not sure what you are really objecting to here.
  19. natasa778

    natasa778 Senior Member

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    Kurt, I am objecting to 'genetic involvement' on the basis that every single thing on the face of the planet has a genetic involvement. So it is meaningless. Of course every disease there is and there every will be has a genetic component. Every predisposition to everything has a genetic involvement. That does not mean that a disease has a 'genetic basis'....
  20. cfs since 1998

    cfs since 1998 *****

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    It does, actually.

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