Chronic Fatigue – XMRV?

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Back in In the issue of 23 October 2009, Science published a study by Lombardi et al. purporting to show that a retrovirus called XMRV (xenotropic murine leukemia virus-related virus) was present in the blood of 67% of patients with chronic fatigue syndrome (CFS) compared with 3.7% of healthy controls.[1]

This as everyone will recall, attracted a great deal of scientific and patient derived interest, but there has been considerable lack of success in the replication of these findings by other investigative groups.

Two recent studies suggest that the relationship is not one of a causal association, but one of contamination.[2],[3]

The indication from these reports is that the findings of the XMRV retrovirus in cultures is due to its transfer by recombination of two mouse derived leukaemia viruses during a human prostate tumour graft back in the 1990’s.

Whilst this story still has some legs, and the main scientists still have faith in their original findings, and of course many patients hoped for a simple cause and effect outcome – with subsequent opportunity for resolution, I suspect that this may soon falter as a serious hypothesis.

The US National Institute of Health is sponsoring additional carefully designed studies to ascertain whether the association between XMRV and CFS can be confirmed. I am sure that like me, there are many who will look forward to their findings.

References


[1] Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, Mikovits JA.Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science. 2009 Oct 23;326(5952):585-9. Epub 2009 Oct 8. View Full Paper

[2] Knox K, Carrigan D, Simmons G, Teque F, Zhou Y, Hackett J Jr, Qiu X, Luk KC, Schochetman G, Knox A, Kogelnik AM, Levy JA. No evidence of murine-like gammaretroviruses in CFS patients previously identified as XMRV-infected. Science. 2011 Jul 1;333(6038):94-7. Epub 2011 May 31. View Abstract

[3] Paprotka T, Delviks-Frankenberry KA, Cingöz O, Martinez A, Kung HJ, Tepper CG, Hu WS, Fivash MJ Jr, Coffin JM, Pathak VK. Recombinant origin of the retrovirus XMRV. Science. 2011 Jul 1;333(6038):97-101. Epub 2011 May 31. View Abstract

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5 Comments. Leave new

  • There has been no evidence presented by anyone that the results are due to contamination. Also, the study that claims to found the origin of XMRV, is flawed and presented little facts. They actually didn’t prove the existance of one of the viruses they claim is ancestral to XMRV, they don’t know if the mice they found the viruses are in were used in creating the cell line. They did detect env sequences of XMRV in the earlier xenografts and then based their conclusions on a assay for which they had not determined the sensitivity of. Also, the sequences in the GenBank prove it is not contamation as the diveristy is too large to be from the virus in the cell line, which is probably the XMRV clone, VP-62, that has contaminated their experiments. You are also ignoring the link to prostate cancer.

    Reply
    • Hello Dev
      As I understand the situation to date – some 10 studies have been conducted that have reported a failure to detect XMRV in independent population of patients diagnosed with CFS. The two reports I mention in my news item add additional weight to the opinion that contamination of samples, rather than the causal presence of XMRV is the explanation of exposure.

      The Paprotka study uses a combination of sequencing, phylogenetic and probability analysis to conclude that contamination by XMRV of a particular cell line (22Rv1) derived from the early graft experiments is a realistic explanation. The second looked at 61 CFS patients from the same clinic that had supplied patients for the original Lombardi paper, and found no nucleic acids, infectious virus or virus specific antibodies related to XMRV in the samples.

      Whilst no one, except the highly motivated on either side of the argument is prepared to commit fully to the position of inclusion/exclusion of XMRV as a causative factor in the development of CFS, there is a lack of supportive evidence for the Lombardi paper, and after a while, as per the usual peer review process, this casts doubt and eventually collects stronger numbers of supporters.

      Lets hope that the NIH studies offer some clarity for everyones benefit.

      Reply
  • 10 studies that used unvalidated assays. None of those papers showed their assays could detect clinical positives. You would have this if you were looking for say Hep C, HIV, etc. Pretty predictable if you only guess that your assays will work. There are actually about 10 positive papers about to be published. About half of those have been presented at conferences.

    Paprotka did not sequence PreXMRV-1 from a single source using specific primers, they did not screen the earlier xenografts with an assay that had a proven sensitivity, they did detect XMRV env in the earlier xenografts, the mice containing the two viruses (one that does not exist) have never been shown to have been used in creating 22Rv1, so the idea the 22Rv1 could be the source is missing evidence.

    So no Paportka et al. didn’t use sequencing, phylogenetic and probability analysis. They made a guess and who knows how they got that into Science.

    Knox et al. also didn’t use validated assays. How did they get hold of the patients records is also very interesting. Knox was I believe fired from the WPI, so it would seem there is a conflict of interest.

    It really isn’t appropriate to talk about XMRV, especially when the XMRV Coffin says was created in 22Rv1 is only one strain. Take a look at the GenBank, there is a 5% diversity in strains in there. They have never been found in that cell line. RKO cells have also been found to be infected with that XMRV strain and 293t cells are infected with another human gammaretrovirus that is like XMRV. If it was created in a cell line, it was not a rare event, and it would be unsafe to assume the source had been found, but the evidence is missing. Then there are the polytropic and modified polytropic strains that the WPI recently added to the GenBank, which confirm Lo et al. There is no explanation for those variants either. Coffin also doesn’t have any comment to make on the serology results, or the EM of the immature virion. Who knows what is motivating this strange behaviour.

    The Lipkin study is hardly going to do anything, after all it is only putting one lab to the test. Not the CDC who cannot find the virus again. Remember they did retest 20 WPI positives, found no virus and no contamination. They also switched assays in the blood working group after detecting XMRV in samples, with no contamination.

    It all points to human gammaretroviruses circulating in the population and with so much mouse contamination in labs, we really should start to investigate whether scientist are responsible to creating any of these variants.

    Reply
  • I have to agree with Dev. Not only did the negative studies use unvalidated assays, they used a completely different patient cohort. CFS by any definition is a diagnosis of exclusion that can be applied to anyone who is depressed, burnt out, or has a misdiagnosed fatiguing condition that is not comparable to the WHO classified neurological disease Myalgic Encephalomyelitis (M.E.).

    The patients that WPI/NCI/CC studied met the Canadian criteria for WHO classified M.E. (aka CFS), and were severely ill with evidence of serious neurological and immune dysfunction. Anyone can collect a group of fatigued patients, claim they have CFS, use an unvalidated assay which will not find evidence of any MLV, and get that past peer review. The average person following this farce can see this is not objective science.

    As studies continue, more retroviral sequences are being added to GenBank, showing the expected diversity of MLVs. This cannot be contamination, which the authors of positive studies tested for and ruled out. The fact that XMRV+ patients being treated with ARVs are recovering is proof of the causal theory. What that leaves is the politics – that M.E. was covered up by the creation of CFS because the evidence of abnormal brain scans and immune dysfunction pointed to retroviral infection, a second retroviral pandemic while AIDS was out of control.

    The history of this epidemic disease demonstrates that ME was politically displaced by the psychiatric creationism of CFS for monetary reasons. Scientists can be bought for their opinions or follow popular consensus, whatever keeps them funded. The average person knows that the business of disease is far more profitable than cures. Doctors have lost their objectivity and blindly hand out the latest drugs despite the side effects, or bow to the psychiatric mandate of what constitutes a disease, its cookbook medicine and its a disgrace.

    There is something fundamentally wrong in the field of medicine, and why medical science is being controlled by state-sanctioned psychiatry is the key to why there is so much manufactured controversy about M.E. and similar neurological diseases. Its much easier to follow the consensus and not question the prescribed script, it keeps your job safe. Safe, until its you that needs medical help for a disease they claim does not exist. Science vs psychiatry at its worst.

    Reply
  • Important note: psychiatry is being given more political power over science. In the revision of the DSM – the bible for psychiatric creationism – which is to be aligned with the WHO International Classification of Diseases, there is an alarming new category: Complex Somatic Symptoms Disorder, that was designed to capture anyone suffering the multiple systemic dysfunction of M.E., but it goes further.

    A CSSD diagnosis can be slapped on anyone diagnosed with uncontroversial diseases like heart disease, cancer or diabetes etc. Any psychological reaction that would be a normal response to being ill and possibly being unable to work, meaning less money and more stress, will now ensure that you are automatically given a bolt-on diagnosis of a psychiatric disorder – and that will stay in your medical file forever.

    Reply

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