Research, another negative XMRV study, 17 August 2011

August 18, 2011


From the Journal of Virology, published on line ahead of print on 17 August 2011

J. Virol. doi:10.1128/JVI.00827-11

Copyright © 2011,American Society for Microbiology and/or the Listed

Authors/Institutions. All Rights Reserved.

Phylogenetic analysis of MLV sequences from longitudinally sampled Chronic Fatigue Syndrome patients suggests PCR contamination rather than viral evolution

Aris Katzourakis1, Stéphane Hué2, Paul Kellam2,3, and Greg J. Towers1,*

1 Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK
2 MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland St, London W1T 4JF, UK
3 Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK

* corresponding

Abstract

Xenotropic murine leukemia virus (XMRV) has been amplified fromhuman prostate cancer and chronic fatigue syndrome (CFS) patientsamples. Other studies failed to replicate these findings andsuggested PCR contamination with a prostate cancer cell line,22Rv1, as a likely source. MLV-like sequences have also beendetected in CFS patients in longitudinal samples 15 years apart.Here we test whether sequence data from these samples are consistentwith viral evolution. Our phylogenetic analyses strongly rejecta model of within-patient evolution and demonstrate that thesequences from the first and second time points represent distinctendogenous murine retroviruses suggesting contamination.

12 thoughts on “Research, another negative XMRV study, 17 August 2011”

  1. As there were no patients used in this study it is not a negative paper. It was attempting to look at the findings of Lo et al. and see if they could make them into contamination.

    To do this they constructed a phylogenetic tree of the limited data so far, something that will bias the results, and then they looked at the sequences as if they would behave like HIV. But as Ruscetti and other eminent scientists have pointed out, HGRVs do not behave like HIV. There is certainly nothing abnormal about that, which Towers will be aware of. When you then compare the viruses Lo et al. found to more suitable ones, it is nothing like contamination.

    Towers should now attempt to replicate the successful methodology from the other positive studies. Why is he avoiding this? It is what Ruscetti would say he should do.

  2. I bet most of those who voted “Probably not” in the recent survey on this subject on this MEA website were veteran sufferers. I am talking 20 years or more. Time to let go I think.

    1. What scientific evidence are you offering to say it should be abandoned? Nothing has been presented to show the virus is anything but a real infection in humans? Contamination is only a belief.

      Human gammaretroviruses have been shown to be integrated.
      They are producing an immune response (which cannot be contamination)
      There are EM’s of the virus budding from human cells and maturing. (which cannot be contamination)
      The virus has been shown to be infectious.
      The virus is found in a much higher proportion of patients than controls.
      The virus has been isolated.

      All that is left if pathogenesis, which will need a clinical trial.

      These are Koch postulates, which cannot be fulfilled for other retoviruses.

      1)A nucleic acid sequence belonging to a putative pathogen should be present in most cases of an infectious disease. Microbial nucleic acids should be found preferentially in those organs or gross anatomic sites known to be diseased, and not in those organs that lack pathology.
      2)Fewer, or no, copy numbers of pathogen-associated nucleic acid sequences should occur in hosts or tissues without disease.
      3)With resolution of disease, the copy number of pathogen-associated nucleic acid sequences should decrease or become undetectable. With clinical relapse, the opposite should occur.
      4)When sequence detection predates disease, or sequence copy number correlates with severity of disease or pathology, the sequence-disease association is more likely to be a causal relationship.
      5)The nature of the microorganism inferred from the available sequence should be consistent with the known biological characteristics of that group of organisms.
      6)Tissue-sequence correlates should be sought at the cellular level: efforts should be made to demonstrate specific in situ hybridization of microbial sequence to areas of tissue pathology and to visible microorganisms or to areas where microorganisms are presumed to be located.
      7)These sequence-based forms of evidence for microbial causation should be reproducible.

      1, 2, 5, 6, 7 have all been met. 3 and 4 would need a clinical trial and assays that can measure the viral load.

  3. Dear Jot, didn’t say “should” or “abandoned”. I am “letting go”. However, I am not convinced M.E. is caused by any virus but that most of us pick up one or another of them permanently because of central nervous system damage and malfunction by other organic invaders such as, perhaps, chemicals. This view formed by bodily experience of 25 years and reading most theories from multiple sources.

    1. The damage would have to be caused by something in the first place and a retrovirus would do this and account for the reactivating viruses we do see in patients. This hypothesis is draw from what we know about ME, human and mouse viruses.

  4. Since I cant get access to read the whole paper (without paying), I cant comment on this paper.
    The abstract does not give sufficient detail on the reasoning leading to these conclusions.

    However I am continually struck by the ease with which negative papers are published, when ones that support the WPI and Ruscetti never reach the public.

    I remember, however, the verdict of Dr Snyderman, who is XMRV positive and who has lived a further 9 months, something he attributes to taking antiretrovirals for his leukemia and XMRV.

    Why are some researchers so keen to ignore important evidence which shows that a retrovirus could be causing our disease, and that treatments may already be possible?
    Can their motivation be good? Do they care about the patient?
    I doubt it.

    If the arguments of these negative papers were accepted, no-one would ever be able to prove they had found an animal virus in humans. Preliminary research would be blocked before a coherent picture could be drawn.

    The burden of proof is raised to an impossible level.
    (Perhaps that is the motive)

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