The perplexing condition known as chronic fatigue syndrome (CFS) might be linked to infection with a retrovirus, report the authors of a new paper published this week in Proceedings of the National Academy of Sciences (PNAS). The association is not new, but the researchers reportedly asked the journal to delay publication of their study, which had been accepted in May, after the online publication of conflicting conclusions July 1 in Retrovirology.

The researchers noted that they held the paper, which had already been peer reviewed, to reassess the findings. "My colleagues and I are conducting additional experiments to ensure hat the data are accurate and complete," wrote co-author Harvey Alter of the National Institutes of Health, in an email statement to The New York Times last month. "Our goal is not speed, but scientific accuracy," he wrote.

The journal also stood by the decision. "As a publisher, when authors or their funding agencies request additional time to ensure that work is ready for public release, particularly when there are public health implications, we strive to work closely with them to promptly address their concerns," wrote the journal's editor in chief, Randy Schekman, in an editorial in the same forthcoming issue of PNAS. But the delay proved too long for many, causing a small uproar from patients, advocates and others, leaving Schekman, "inundated by emails from people with chronic fatigue syndrome begging us to release the paper," he told the Times in July.

The syndrome has been difficult to diagnose. Physicians often choose it as a label for a collection of symptoms (including tiredness, headaches and immune system abnormalities) that cannot be readily attributed to any other disease. Researchers estimate some 17 million people globally have CFS.

The retrovirus group in question, murine leukemia virus- (MLV) related viruses, includes xenotropic murine leukemia virus–related virus (XMRV), which has also been linked to prostate cancer.

The retrovirus became implicated in CFS in a paper published in October 2009 in Science. The authors, led by Vincent Lombardi of the Whittemore Peterson Institute in Reno, NV, found that some 67 percent of people with the syndrome seemed to harbor XMRV, as compared with 3.7 percent of healthy volunteers who did.

The new work in PNAS produced similar results. Alter, study leader Shyh-Ching Lo of the Food and Drug Administration's Tissue Microbiology Laboratory,  and  their colleagues tested blood samples from 37 patients with CFS and 44 healthy volunteers ands found genetic traces of an MLV-like virus in more than three quarters of the CFS patients (86.5 percent) and only three of the volunteers (6.8 percent).

But the new findings will not likely be the final word in the debate. Four recent studies—including the one published last month in Retrovirology—came up empty handed when searching for a correlation between CFS and XMRV or genetic markers of a similar retrovirus.

Scientists and patients might not have a definitive answer about the prevalence of retroviruses in CFS patients until researchers can show "the integration of the viral genes into the human genome," Lo's team wrote in its study. The group noted that the contradictory evidence coming out of labs might be  the result of geographic or patient recruitment differences. Other researchers, however, think that a geographical explanation would be "baffling," as noted by a group, led by Valerie Courgnaud, of the Institutde Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifiue in France, in a commentary published in the same issue of PNAS.

And as Lo's team explained in its study, even if more research confirms a higher rate of retroviral infection in people with CFS, that will not mean MLV-related viruses cause the syndrome. The correlation "could reflect an increased susceptibility to viral infections due to an underlying CSF-related immune dysfunction, rather than a primary role for these viruses n the pathogenesis of CFS," the researchers noted in the paper.

In fact, it might take a new treatment to clarify the role of these retroviruses in CFS. And some researchers think the time is right to start looking into drugs that fight against retroviruses, known as reverse-transcriptase inhibitors (as have been investigated to address XMRV in prostate cancer). "Studies to establish proof of principle are justified to determine whether safe antiviral regimens can impact on CFS and to determine whether xenotropic or polytropic MLV is causally associated with this debilitating disease," concluded Courgnaud and her colleagues.

Image courtesy of iStockphoto/netris