‘Origins of XMRV deciphered, undermining claims for a role in human disease’, National Institutes of Health, 2 June 2011

Press release issued on 2 June 2011 by the US National Institutes of Health.

Delineation of the origin of the retrovirus known as XMRV from the genomes of laboratory mice indicates that the virus is unlikely to be responsible for either prostate cancer or chronic fatigue syndrome in humans, as has been widely published. The virus arose because of genetic recombination of two mouse viruses. Subsequent infection of lab experiments with XMRV formed the basis of the original association.

Reporting in Science, Vinay Pathak, Ph.D., and his research team from the National Cancer Institute (NCI), part of the National Institutes of Health, in collaboration with other researchers, described experiments that provide an understanding of when and how XMRV arose and explain the original, incorrect association. XMRV stands for xenotropic murine leukemia virus-related virus.

This study is being reported in the same issue of Science as another study of XMRV (Knox et al.) that finds a lack of association between the virus and CFS even in the same patients from a 2009 study. “Taken together, these results essentially close the door on XMRV as a cause of human disease,” said John Coffin, Ph.D., special advisor to the NCI director, and professor at Tufts University School of Medicine, a coauthor of the paper with Pathak.

Murine leukemia viruses are retroviruses that cause cancers and other diseases in mice. They are divided into different classes, one of which is xenotropic murine leukemia viruses. Although viruses in this class cannot grow in or infect cells from most mice, in the laboratory they can infect cells from other species, including human cells.

XMRV was first reported in samples from a human prostate tumor in 2006, and has been reported to be present in 6 percent to 27 percent of human prostate cancers. Later research reported XMRV in the blood of 67 percent of people with CFS.

The assertion that XMRV is circulating in the human population has been challenged by several studies that have failed to detect XMRV in multiple sets of specimens from people with prostate cancer or CFS and healthy controls.

To try to resolve the degree of association between XMRV and human disease, Pathak, who led these studies at NCI in its Viral Mutation Section, Coffin, and their colleagues examined human prostate cancer cells which contained XMRV, as well as the tumors from which these prostate cell specimens arose after they were grafted into mice. Grafting human tumors, called xenografts, into mice is a common way to study disease when it might be unsafe to test new treatments or methods in humans.

Upon careful examination in this new study, it was shown that initial prostate tumor xenografts did not contain XMRV but later tumors that had been derived from them did, demonstrating that XMRV was not present in the original human tumor as previously supposed. Instead, the virus appears to have infected tumor cells while they were in mice. In addition, the mice that were used for xenografting the prostate tumor cells contained two previously undescribed viruses, PreXMRV-1 and PreXMRV-2. Each of these viruses has a stretch of over 3,200 nucleotides, the basic building blocks of DNA, which is nearly identical to XMRV, differing by only a single nucleotide.

Genetic comparison of the PreXMRV-1 and PreXMRV-2 sequences revealed that each one has non-overlapping stretches that are nearly identical to XMRV. Pathak, Coffin, and their colleagues postulate that recombination between these viruses generated XMRV in human cells while the cells were being grown in a mouse sometime between 1993 and1996 and infected the prostate tumor cells. Recombination between virus genomes in a cell infected by more than one virus is common.

Based on this genetic analysis, the scientists concluded that XMRV was not present in the original prostate tumor samples but arose only after they had been put into mice. The probability that an identical recombination event occurred independently is about 1 in 1 trillion, making it extremely unlikely that XMRV arose from another source. The researchers concluded that the association of XMRV with human disease is due to contamination of samples with virus originating from this recombination event.

“After the reports of XMRV in human prostate cancer, and later of XMRV in people with CFS, retrovirologists all over the world were excited to explore its role in human infection and disease. The results published today are not what we would have expected, but due to the time and resources dedicated to the understanding of this virus by researchers at NCI and NIH as well as others, scientists can now concentrate on identifying the real causes of these diseases,” said Pathak.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at www.cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

References:

Paprotka et al. Recombinant Origin of the Retrovirus XMRV. Online Science. May 31, 2011.

Knox et al. No Evidence of Murine-like Gammaretroviruses in CFS Patients Previously Identified as XMRV-infected. Online Science. May 31, 2011.

For a Q&A on XMRV, please go to http://www.cancer.gov/newscenter/qa/2011/xmrv_qa.

5 thoughts on “‘Origins of XMRV deciphered, undermining claims for a role in human disease’, National Institutes of Health, 2 June 2011”

  1. The origin of XMRV has not been found. This idea is also not able to explain the other strains of the virus.

    It can also be hypothesised that the two viruses they claim to be preXMRV-1 and 2 are decendants of XMRV There is no data to suggest which is correct, so the conclusions are unsafe for that reason alone. There is also no information of whether the lab mice containing these viruses were even used in the creation of the cell line, they want to pin a contamination story on. They have also failed to check wild mice for these viruses, so again the conclusions are unsafe. Finally, thelater generations of the cell line were treated with testosterone, wich XMRV is responsive to. This massive increase in viral titre would have made it much easier to detect the virus, then in the earlier generations where the virus would be at normal low levels. Thus they need to clinically validate their assays and failed to do so. No proof exists that the virus is not in the earlier generations.

  2. I think it is absolutely amazing how they can trace things like this back through – well – time really.

    Imagine how this science can transform our understanding… cool or what?!

    Not that I can even pretend to understand the actual inner-workings… merely an observer I suppose… can’t even understand the Financial Times any more…

    1. They didn’t trace it back. They only have two viruses, which they haven’t checked for in wild mice, that have sections that are like XMRV. They have no idea if they are pre or post XMRV. They are also not able to explain the other strains.

  3. Modern scientific techniques are miraculous, aren’t they – though I don’t understand a fraction of what goes on.
    However, no-one has yet explained the presence of anti-bodies to XMRV.
    The other notable aspect is how much time, effort and money have been expended on trying to ‘debunk’ XMRV as opposed to finding the causes of ME along with some treatments.
    A sad comment on the scientific community when such negativity consumes all the resources and blocks the development of beneficial research.

    1. Not miraculous in this case. They have not proven they have found origin of XMRV. The paper is totally rubbish and should never have been published.

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