Study reignites debate over virus’ role in chronic fatigue


Government scientists have found traces of a mouse-related virus in 86% of patients with chronic fatigue syndrome, a discovery that is likely to reignite the controversy surrounding the virus widely known as XMRV.

Nevada scientists first reported the presence of the virus in chronic fatigue patients in 2009, but at least three subsequent studies failed to detect it. On Monday, however, researchers from three different government agencies said they had found the virus in stored and fresh blood samples.

“There is a dramatic association with chronic fatigue syndrome ... but we have not proven causality for the agent,” said Dr. Harvey Alter, chief of clinical studies at the National Institutes of Health Clinical Center and one of the authors of the new report, speaking at a news conference. The report was posted online ahead of its publication in the Proceedings of the National Academy of Sciences. “The dilemma now is how to reconcile that some labs find the association and some don’t.”

Coauthor Steve Monroe, director of the division of high-consequence pathogens and pathology at the Centers for Disease Control and Prevention, conceded that “these results do raise as many questions as they answer. There are still a lot of things about this virus that we don’t know.”

Researchers hope some of those questions will be answered within the next year or so. The government is sponsoring a number of studies to determine, among other things: whether the virus is, in fact, present in many or most chronic fatigue patients; whether researchers can find antibodies against it in such patients; whether a standardized test for the virus can be developed; how common the virus may be in the blood supply; and whether it can be transmitted through blood donations.

In an editorial accompanying the report, French and Canadian researchers called for clinical trials to determine whether chronic fatigue patients can be treated with anti-AIDS drugs that have been shown to block replication of the virus in a test tube. Desperate patients have already begun taking the drugs despite a lack of proof that the virus is even related to their symptoms.

Alter cautioned that all of the questions surrounding the virus would remain controversial “when not everybody finds the same thing. Very good laboratories have come up with disparate results,” and no one is sure why that is so. It may be due to differences in laboratory testing or, more likely, because of differences in patient populations. It is also possible that there is more than one cause of chronic fatigue syndrome.

The illness itself has a long history of controversy. Thought to affect at least 1 million Americans and 17 million people worldwide, it is characterized by debilitating fatigue, chronic pain and depression, among other symptoms. But because there are no biochemical markers to identify it, some physicians still argue that it resides mostly in the minds of patients; activists contend that the CDC and other government agencies have refused to study the disease adequately.

Xenotropic murine leukemia virus-related virus, or XMRV, was first discovered — in some human prostate tumors — four years ago. That study has been only partially replicated, and the link to tumors is also controversial.

In October 2009, researchers from the Whittemore Peterson Institute for Neuro-Immune Disease in Reno reported that they had found the virus in 68 of 101 blood samples from chronic fatigue patients, but in only eight of 218 healthy patients.

This summer, however, three separate groups of researchers reported that they could not replicate the Whittemore Peterson findings. The first two negative results were from Europe, and some experts speculated that there might be different patient populations involved. But the third study, from CDC researchers, involved American patients.

The study reported Monday had already been accepted for publication in the Proceedings of the National Academy of Sciences when the CDC study was published in July. The current study’s authors requested a delay in publication while they tried to resolve conflicts between the two reports. Ultimately, they were unable to do so and publication proceeded.

The team from the CDC, the National Institutes of Health and the Food and Drug Administration studied blood samples from 37 chronic fatigue patients collected in the mid-1990s for a study to determine if the disease was caused by a type of infection-causing bacteria known as mycoplasma.

Mycoplasma was not found and the samples were stored in a freezer. Using sensitive assays, the team found evidence for several virus variants in 32 of the 37 samples and in three of 44 (7%) samples from healthy patients. Fresh samples from some of the patients showed the same viruses.

“We’re delighted,” said Judy A. Mikovits, the lead researcher at the Whittemore Peterson Institute. “This is the first group that attempted to replicate the study using our methods.” She said her group would present additional positive findings at a meeting in Washington in two weeks.

The key difference in the new study is that the government team found viruses that appeared to be polytopic. That is, they can replicate in more than one species, including mice and humans. The original virus isolated in Nevada was xenotopic — it could grow in humans but not in mice.

Alter noted that, since the original discovery, the Whittemore Peterson group has isolated the virus, grown it in culture and identified antibodies against it in humans.

Dr. Shyh-Ching Lo, director of the FDA’s tissue safety laboratory program and a coauthor of Monday’s report, said his team had not yet been able to isolate the virus. “We have tried very hard, but that has not been accomplished.”