XMRV research at Emory University, Atlanta

By Martha Nolan McKenzie:

In early September, a group of scientists, physicians, and epidemiologists gathered at the National Institutes of Health headquarters for the 1st International Workshop on XMRV—a recently discovered retrovirus that has generated considerable controversy due to conflicting findings regarding its possible link with prostate cancer.

While the conference did little to dispel the disparities between the scientific camps finding evidence of XMRV in prostate cancer samples and those finding none, it did establish who a leader in the search for answers would 
be, Emory. “One thing that became very clear at the conference is that Emory is at the epicenter of XMRV issues,” says Raymond Schinazi, professor of pediatrics 
and chemistry at Emory’s Center for AIDS Research and 
a conference attendee.

This cunning retrovirus may well need such a powerhouse to wrest its secrets. XMRV—or xenotropic murine leukemia virus-related virus—was first identified in prostate tumors in 2006 by researchers at the Cleveland Clinic and University of California at San Francisco. Their study found XMRV present in 40% of prostate tumor samples of one phenotype and in 1.5% of samples of two other phenotypes. However, subsequent studies by other labs, including a study of 800 prostate cancer cases by researchers at Johns Hopkins, found no evidence of the retrovirus. XMRV also has been linked with chronic fatigue syndrome, with similarly conflicting results. A group of CDC researchers couldn’t find XMRV or related viruses in patients with chronic fatigue syndrome (CFS) or healthy controls, but an FDA and NIH team did.

In 2008, in an attempt to get to the bottom of the divergent findings, the CDC enlisted multiple academic centers to study the retrovirus, supplying many with prostate cancer samples from the vast archives of John Petros, an Emory urologist. “I’ve been doing prostate cancer research for 17 years, and I’ve accumulated thousands of specimens from hundreds of patients,” says Petros. “I had never heard of XMRV when the CDC approached me about using some of my samples for its study. But it made me wonder whether I should start looking into it, so I turned to my a colleague who knows everything about retroviruses for advice.”

That colleague was Emory scientist Dennis Liotta, who along with Schinazi in 2005 developed a major new AIDS drug, Emvitra, earning the university the largest licensing fee awarded at the time. Liotta not only convinced Petros to pick up the study of XMRV, he funded his lab and four others. “That was huge,” says Petros. “You couldn’t get grant support for it at that time because it was too novel for the NIH. Only one grant had been funded, for the University of Utah. Even Robert Silverman [the Cleveland Clinic researcher who originally identified XMRV] had not gotten his grant funded yet.”

At the same time, but independent of the Liotta-funded labs, Schinazi began collaborating with Ila Singh, the University of Utah pathologist who had garnered the only NIH grant. In addition, Abbott Diagnostics contacted Francois Villinger, a pathologist at Emory’s Yerkes National Primate Research Center, to develop a nonhuman primate model of the retrovirus. In all, seven labs at Emory are studying XMRV.

Developing a reliable, repeatable test

The first order of business for Emory researchers was to develop an effective diagnostic test to identify XMRV. 
 “We cannot as a scientific community begin to answer the basic questions of XMRV transmission, frequency in the population, association with disease, etc., until we can effectively test for infection,” says Petros. “If this virus, in fact, promotes prostate cancer and CFS, we need to be able to screen the blood pool and organ donors for it to prevent transmission.”

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