Two years ago, a research team in Nevada linked an exotic mouse virus to chronic fatigue syndrome, sparking hopes among patients that a cause of the baffling condition had finally been found.
But two other research teams reported Tuesday that the virus, called XMRV, is a laboratory contaminant incapable of infecting human blood.
“This virus cannot establish infections in humans,” said Jay Levy of the University of California at San Francisco, author of one of the new reports in the journal Science. “If it’s detected, it’s a result of contamination.”
Working with scientists at virus laboratories in Illinois and Wisconsin, Levy retested the blood of 43 patients who had tested positive for XMRV. Although the team searched with a variety of advanced methods, it found no signs of the virus.
When Levy added XMRV to blood from patients and from healthy people, immune system components of the blood quickly disabled the virus. “There wouldn’t be any time for the virus to establish infection,” Levy said.
The second report released by Science adds to growing suspicions that XMRV contaminates a wide range of solutions and other laboratory products used to test blood for viruses. Led by Vinay K. Pathak at the National Cancer Institute, the report concludes that XMRV was accidentally created in a laboratory working with human cancer cells in the mid-1990s.
Although it remains unknown in which laboratory the accident occurred, when human prostate cancer cells were engrafted into laboratory mice, two viruses in the DNA of the mice joined to form XMRV, Pathak concluded after a detailed analysis of the genetics of the virus.
Further, the strains of XMRV purportedly found in patients are virtually identical to the strain Pathak found in the prostate cancer cells that had been grown in mice. If XMRV had been hopping from person to person, it would have changed over time.
Levy also found XMRV in laboratory products used to test for viral DNA. And a 2010 study from an English team, published in the journal Retrovirology, reported evidence that XMRV is a laboratory contaminant.
“I don’t know how you can see it any other way except that this virus came from a lab mouse,” said Vincent Racaniello, a virologist at Columbia University who was not involved in the XMRV research.
In 2006, XMRV first popped up in scientific circles as a possible risk factor for prostate cancer. Researchers led by Joseph DeRisi at the University of California at San Francisco reported finding the virus in human prostate tumors.
In light of the newly uncovered lab-mouse origins of XMRV, those findings are in question, too, Racaniello said.
In 2009, the original report linking XMRV to chronic fatigue syndrome was hailed by patients as a breakthrough. The study found signs of the virus in the blood of 68 of 101 patients.
The report set off a wave of intensive international research and last year prompted the Red Cross to stop accepting blood donations from anyone diagnosed with the condition.
But the new reports may be a denouement, putting to rest the notion that XMRV causes chronic fatigue syndrome, a condition that affects an estimated 1 million to 4 million people in the United States. At its worst, the condition is debilitating.
At least 10 other studies have failed to find XMRV in chronic fatigue syndrome patients.
The 2009 study was published by Vincent C. Lombardi and Judy A. Mikovits of the private Whittemore Peterson Institute in Reno, Nev. The new reports prompted the journal Science to ask the pair to retract their results.
In an “expression of concern,” the journal’s editor, Bruce Alberts, wrote that the validity of the original study is now “seriously in question.”
But Lombardi and Mikovits are refusing to retract their study. They are “extremely disappointed” in Science’s actions, the Whittemore Peterson Institute said in a statement.
In 2010, a diagnostic services company, VIP Dx, also in Reno, paid the Whittemore Peterson Institute a licensing fee for an XMRV blood test. The Web site of VIP Dx stated on Tuesday that high demand is slowing processing of the tests.
Because XMRV is a retrovirus like HIV, many patients have prematurely rushed to take anti-HIV medications, said Konstance Knox of the Wisconsin Virus Research Group in Milwaukee, who worked with Levy. But “there is no basis for these kinds of medications to be prescribed and taken by this patient population,” Knox said.
A new effort to screen 150 chronic fatigue patients for XMRV, funded by the National Institutes of Health, is just getting underway. Researchers and patient advocates expect the study to be the last word on the topic, as blood samples from patients and healthy volunteers will be blindly screened at three laboratories.
Levy, however, called for the new study to be scrapped. “As far as I’m concerned, our study should put the whole issue to rest,” he said.
But Ian Lipkin, the Columbia University virologist heading up the NIH-funded effort, said Tuesday that he received confirmation from the director of the NIH, Francis Collins, that the study will proceed.
“There’s nothing published today that changes our commitment to seeing the project to completion,” said Lipkin.