Viral cause for chronic fatigue?

 

A recently-discovered virus found to be associated with prostate cancer has now been linked to chronic fatigue syndrome (CFS), according to a study published online in Science today (8 October). The study, although only correlative, lends a greater immediacy to questions about how the virus is spread and what, if any, other diseases it might cause.

XMRV Image: Whittmore Peterson Institute

"Either [the virus] is a causative factor or it's a marker of patients who cannot clear the virus," Eugene Kandel, a molecular biologist at Roswell Park Cancer Center who was not involved in the study, told The Scientist. The study doesn't distinguish between the two possibilities, he said. The virus, awkwardly named xenotropic murine leukemia virus-related virus (XMRV), may simply be a passenger, more prevalent in patients with underlying disease.

Doctors and researchers still debate whether CFS is a disorder with physiological causes and what those causes might be. A number of causes have been proposed for CFS, including chronic inflammation, genetic predisposition, and stress. The disease is estimated to affect 1% of the world's population, and a number of viruses, including some herpesviruses and enteroviruses, have been proposed as triggers of the disease.

Here, the researchers found XMRV in 67% of samples from patients with chronic fatigue syndrome out of 101 samples analyzed, compared to approximately 4% of 218 control samples. Researchers also found antibodies to XMRV in the serum of the infected patients, suggesting that patients mounted a specific immune response to the virus.

XMRV, a retrovirus with close homology to the cancer-causing mouse virus, murine leukemia virus (MLV), was first discovered in 2006 by researchers tracking down an enzyme that was mutated in prostate cancer patients. The enzyme had both tumor suppressor and antiviral properties, which suggested the possibility that prostate cancer had an infectious cause. When researchers scanned tissue from prostate cancer patients for viral infection using a specially-designed virus chip, they pinpointed XMRV.

Robert Silverman of the Lerner Research Institute at the Cleveland Clinic, a coauthor of the Science paper, said that a larger-scale epidemiological study would have to be done to strengthen the observed correlation. Researchers will also need to explore the basic biology of the virus, such as how it is transmitted, what host factors might restrict its growth, and what other species it might infect, he added.

To date, only 12 records appear in a PubMed search under the term XMRV, but that is likely to change. "A lot of people are working on this virus," said Silverman, who was part of the team that first discovered it. "I know, because I've been giving it out to a lot of labs."

The researchers also noted that if the study's 4% of control patients infected with XMRV were to be extrapolated to the general population, millions of Americans could be carriers of the virus. This is worrying, said Silverman, because XMRV belongs to a family of viruses that cause neurological disease.

It also raises concern in patients undergoing gene therapy, in which MLV is often the viral vector delivering the genes. Kandel and Silverman recently published a study showing that cells containing non-infectious MLV vectors could regain their ability to replicate and infect other cells when co-infected with XMRV. This could be problematic because "we make vectors that are more aggressive than the natural virus, on the assumption that these viruses can't escape," said Kandel