Fresh doubts about connection between mouse virus and human disease: Science Now blog, 8 March 2011

From Science magazine’s Science Now blog, 8 March 2011 (story by Jon Cohen)

BOSTON – A new finding presented at a conference here last week throws cold water on the impassioned debate about the link between a novel mouse retrovirus and prostate cancer and chronic fatigue syndrome in humans. Yet few believe it will end the controversy, which began in 2006.

In an extensive sleuthing expedition that looked back nearly 20 years, two collaborating research teams contend they have evidence that xenotropic murine leukemia virus-related virus (XMRV) resulted from the chance recombination of pieces of two mouse viruses in lab experiments and that the connections to human disease are spurious. “That nails it,” said retrovirologist Nathaniel Landau of New York University. “Everyone working on this thing has this virus contaminating their stuff. It’s been a tremendous waste of time and money.”

Vinay Pathak, a retrovirologist who works at the HIV Drug Resistance Program run by the U.S. National Cancer Institute (NCI) in Frederick, Maryland, presented the new data at the 18th Conference on Retroviruses and Opportunistic Infections. Pathak explained how he became intrigued by a 2009 study that showed how a human prostate cancer cell line was infected with XMRV. He acquired earlier material made to use the cell line – in particular, tumors grown in mice, called xenografts, that were then “passaged” to other mice—and established that the original human tumor could not have harbored XMRV.

More startling still, Pathak’s lab found that some of the early samples of xenografts did have a stretch of DNA that was nearly identical to about half of the XMRV genome. A group led by John Coffin, who works at both NCI and Tufts University here, made a similar discovery with different samples of xenografts. When the teams compared notes, they saw that the two sequences perfectly overlapped to form XMRV.

“It was an amazing moment, the kind that happens once or twice in a career,” says Coffin. “It was like seeing a puzzle come together.” As Pathak emphasized in his talk, the DNA sequences in what they dubbed preXMRV-1 and preXMRV-2 are nearly identical to the XMRV sequences reportedly found in humans but suspected to be a lab contaminant by some groups. Retroviruses frequently recombine with each other, which is how the two preXMRV sequences likely became XMRV. Now Coffin is convinced that “it is all contamination.”

A longer version of this article will appear in this week’s issue of Science.


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