NIH Research Matters: Study Undermines XMRV Connection to Human Disease

15 Jun

Study Undermines XMRV Connection to Human Disease is an article up on the U.S. National Institutes of Health “Research Matters” site. xenotropic murine leukemia virus-related virus (XMRV) has recently been hypothesized to be involved in chronic fatigue syndrome, prostate cancer and, as you guess from the discussion here at Left Brain/Right Brain, autism.

The discussion below (copied in whole from the NIH website) does not touch on autism, but does give some insight into how the false-positive link to prostate cancer came about, and how the link to chronic fatigue syndrome is not standing up to scrutiny.

The retrovirus previously tied to prostate cancer and chronic fatigue syndrome (CFS) is unlikely to be responsible for either, according to new research. The virus appears to have arisen in the laboratory. The association with human disease was probably due to contamination of samples.

Transmission electron micrograph of round virus particles.
XMRV particles, as visualized by transmission electron microscopy. Photo by Dr. Ila R. Singh, University of Utah

The xenotropic murine leukemia virus-related virus (XMRV) was first found in samples from a human prostate tumor in 2006. It was reported to be present in 6% to 27% of human prostate cancers. A study in 2009 also found XMRV in the blood of 67% of people with CFS. However, these results were challenged by several studies that failed to detect XMRV in samples from people with prostate cancer or CFS.

A research team led by Dr. Vinay Pathak of NIH’s National Cancer Institute (NCI) set out to investigate whether XMRV could have originated in the laboratory. When studying cancer, researchers often graft human tumors onto mice to create what are called xenografts. The scientists examined the process used to create the xenografts as well as the subsequent procedures that led to the identification of XMRV.

In the online edition of Science on June 2, 2011, the researchers reported that the initial prostate tumor xenografts didn’t contain XMRV, but that later tumors derived from them did. The virus appears to have infected the human tumor cells while they were in mice.

Closely related murine leukemia viruses are known to cause cancers and other diseases in mice. In the laboratory, these viruses can infect cells from other species, including humans. The team did a genetic search in the strains of mice previously used for xenografting the prostate tumor cells. They detected 2 previously undescribed viruses, which they dubbed PreXMRV-1 and PreXMRV-2. Genetic comparison of the PreXMRV-1 and PreXMRV-2 sequences revealed that each has a long stretch of DNA that’s nearly identical to XMRV.

The scientists postulate that genetic recombination between these 2 viruses generated XMRV while human prostate tumor cells were being grown in a mouse. The recombination—a common outcome when cells are infected by 2 or more viruses—likely occurred sometime between 1993 and 1996. The recombined virus then infected the human tumor cells.

Another report in the same issue of Science failed to find an association between XMRV and CFS, even in the same patients from the 2009 study. The research team found evidence of sequences from the 2 mouse viruses in commercial laboratory reagents. They concluded that the previous results likely stemmed from laboratory contamination.

“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,” Pathak says. “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.”

“Taken together, these results essentially close the door on XMRV as a cause of human disease,” says coauthor Dr. John Coffin, special advisor to the NCI director and a professor at Tufts University School of Medicine. Some evidence still suggests that these diseases may stem from viruses, but not from XMRV.

6 Responses to “NIH Research Matters: Study Undermines XMRV Connection to Human Disease”

  1. Dev June 15, 2011 at 21:41 #

    The study didn’t not undermine XMRV. There is evidence missing to draw the conclusion that the origin of XMRV is that cell line. It is says nothing about the other variants of HGRVs and nothing about infected humans.

  2. KAL June 15, 2011 at 21:55 #

    Although the evidence that XMRV is not a human pathogen is strong the NIH is continuing to fund additional research at this time. Dr. W. Ian Lipkin, aka the Virus Hunter, currently has two studies involving CFS going. One is looking specifically at XMRV in CFS patients. The other is a metagenomics study looking at a wide variety of viruses in CFS and other diseases.

    According to Lipkin proving causation is particularly challenging in instances where microbes have effects that are remote in time or space, or require cofactors such as coinfection for expression. He also states that implication of agents may be difficult when classical hallmarks of infection are absent or mechanisms of pathogenesis are indirect or subtle.

    He also believes that formal, definitive proof of causation may not be obtained until a specific intervention such as a drug or a vaccine is shown to prevent disease.

    • Sullivan June 15, 2011 at 22:22 #

      I find 18 projects funded by NIH which include the keyword XMRV (not all of them are XMRV studies, some just cite the term). 4 in 2011. I don’t see any with Dr. Lipkin as the principle investigator, but I could be missing something.

      He is involved in XMRV, as is NIH. Here is a quote from a short article in Nature in March

      Others, too, are rallying for a definitive answer. Ian Lipkin, a microbial epidemiologist at Columbia University in New York, has a reputation for getting to the bottom of mysterious disease–pathogen links. His team debunked the association between Borna disease virus and chronic fatigue, for example. Now he is spearheading the $1.3-million effort funded by the US government. He is leaving the testing to three labs: Mikovits’s at the WPI, Alter’s at the NIH and the CDC. Each will receive coded samples of white blood cells and plasma from 150 patients with chronic fatigue and from 150 healthy controls. The labs will test for XMRV using their method of choice. Lipkin will crunch the data and unblind the samples.

      If NIH is coming down strong against XMRV causing disease as in the above article, my guess is that the data coming out from the collaboration between NIH, CDC, WPI and Lipkin is not showing a connection.

      Will NIH fund any more studies? That is the question.

  3. aidan walsh June 16, 2011 at 00:45 #

    getting a little tired of this xmrv hype, i wonder now whether they will start looking for 45% of the hiv virus envelope gene that was reported over 10 years ago…in 2013 they will attempt to label the illness as all in ones head with the w.h.o. and that will never happen…i think they have dragged their feet on cfs and the final truth must be told and someone should accept the full responsibility of total neglect…how many more have to die and how many more lives have to be completely trashed by this chronic illness…to think that all of us have paid tax all our lives and have to be treated like this is a total disgrace and inhumane…sure they will go back and forth on xmrv like a game of tennis not being able to make up their minds and in the mean time patients will continue to be denied proper health care access,clinical trials and there much deserved disibility premiums and to add more to insult they will fund the clowns $millions to downplay the illness saying it is in one’s head and also neglecting serious honest physiological researchers their grants when they are submitted…sincerely aidan walsh southampton, u.k.

  4. John Buettner June 16, 2011 at 04:06 #

    Why is the CDC et al trying so hard to disprove the WPI’s findings?

    If XMRV is due to contamination, then why is is that 67% of ME/CFS patients tested positive, but only 3.7% of healthy controls?

    From the Invest In ME conference held in London on May 20, 2011:

    The final presentation was by Wilfried Bieger (Munich, Germany). He mentioned their earlier studies to detect XMRV, which had been negative. His team had then collaborated with Judy Mikovits and set up a highly sensitive, specific and uncontaminated protocol for virus detection, sequencing of viral DNA and antibody testing with western blot. Viral DNA and RNA were not detected in fresh blood, but after cultivation of PBMCs for 6 weeks under stimulation and using partly co-culture with virus permissive LnCap cells, culture cells turned positive in some patients. Presence of XMRV was confirmed by sequencing XMRV specific DNA. There have been approximately 40% positives so far.

    THIS is what results from properly REPLICATING the study done by WPI, et al: you find XMRV in ME/CFS patients!

  5. aidan walsh June 16, 2011 at 12:35 #

    john burns school of medicine at the university of hawaii have already published replicated science that cfs is linked to ciguatera (epitope) toxins and they also have mentioned certain ways to try and eradicate this infection, WHY?, are we not hearing anything across the web on this and again all we here is xmrv hype and again no replicated proof that xmrv is any cause of any illness…can someone please explain to me WHY?,300 consecutive cfs patients tested positive to the ciguatera assays? it is now my understanding that this work is now somehow connected to ‘low level radiation poison’ and how long again will the nih drag their buts on the ciguatera issue SINCE they knew about this as far back in ‘2003’ and to date have done nothing…all one has to do is now go back and look at the ‘chernobyl’ disaster and you will find patients with identical symptoms of cfids…what now will the nih/cdc do when countless people now in japan come down with cfids like symptoms? I CAN TELL YOU ALL NOW WHAT THEY WILL DO, THEY WILL SAY IT IS ‘STRESS’ AND THEY WILL PUT POSTERS UP ON THEIR WALLS DEPICTING CFIDS PATIENTS AS COMICAL AND LAUGHING ABOUT OUR DAILY SUFFERING…HOW MANY CHILDREN NOW WITH AUTISM ARE GOING TO BE POSITIVES TO CIGUATERA TOXINS…HOW MANY MORE CHILDREN HAVE TO BE FORCED FROM THEIR HOMES BY THE COURTS WITH CFIDS/M.E. TYPE SYMPTOMS…I WILL SAY THIS HEAR LOUD AND CLEAR,PRAY I NEVER RECOVER FROM THIS ILLNESS BECAUSE THE DAY I DO I WILL SEE ALL OF YOU IN WORLD COURT HOUSES…SINCERELY AIDAN WALSH SOUTHAMPTON, U.K. MAY GOD BLESS EVERY CHILD WITH AUTISM,CFIDS AND ALL OTHER TYPE OF ILLNESSES AND MAY HE CARRY YOU ALL DURING THESE DIFFICULT TIMES…

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