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More so than many illnesses, chronic fatigue syndrome (CFS) frustrates those who suffer from it and those close to them, due to its nebulous assembly of symptoms, along with continued controversies over its etiology, diagnosis, treatment and even its nomenclature. Now, the discovery of a familiar retrovirus in many CFS patients could bring new energy to the field—and fresh hope for more specific medical care.
Chronic fatigue is in part a misnomer. The syndrome often has more to do with immune system abnormalities than pervasive tiredness—although the two can go hand in hand. The symptoms range from exhaustion to muscle pain, giving CFS a reputation among some as a "wastebasket diagnosis". The slipperiness of the syndrome is in part because "it's diagnosed based on exclusion," says Judy Mikovits, director of research at the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nev., and co-author of research on the retrovirus findings published online today in Science. Doctors often apply the label if no other explanation can be found for a patient's symptoms, which may be part of the reason it seems to pop up in everyone from overworked career women to continually sick children.
Roughly 17 million people worldwide are thought to have CFS, but given current diagnosis methods, the true number could be much higher or lower. Having a specific virus to look for would make for much more robust tests and possibly even be a step toward treatment. Mikovits's team thinks they have found just such a candidate.
The xenotropic murine leukemia virus–related virus (XMRV), a type of gammaretrovirus, has recently been linked to strong cases of prostate cancer. Like CFS, this cancer involves changes in an antiviral enzyme (RNase L). The prostate cancer discovery, described last month by Ila Singh, an associate professor of pathology at the University of Utah in Salt Lake City, et al. in the Proceedings of the National Academy of Sciences (PNAS), along with a traditionally high incidence of cancer in CFS patients, got Mikovits and her team thinking: Would they find the same retrovirus in people with CFS?
After analyzing biological samples from more than 100 CFS patients for the retrovirus, two thirds of them were found to test positive for the virus—compared with 3.7 percent of 218 healthy volunteers who were screened.
To find the retrovirus, Mikovits and her team studied documented cases, such as CFS outbreaks in a symphony orchestra in North Carolina and in Incline Village, Nev. "We found the virus in the same proportion in every outbreak," she says. But how are people getting this retrovirus? "Ila's work shows that everyone's susceptible," Mikovits says of the PNAS paper by Singh that illustrates the link between prostate cancer and XMRV and shows that the virus is not linked to a genetic mutation.
Experiments in Mikovits's lab proved that the retrovirus can be transmitted via blood by infecting healthy cells drawn from volunteers with material from XMRV-positive CFS patients. Mikovits hopes to soon have a better understanding of how the virus might be transferred in the real world, especially among families. If it, for instance, is like human T-lymphotropic virus type 1 (HTLV-1), it may be communicable through breast milk or if it's like a herpes virus that is common in CFS, it may be passed along to offspring.
Precisely how this virus is related to chronic fatigue, however, remains a mystery. One of the problems with tracking down CFS is that it may not be a single ailment. "We think that the problem is that CFS is a collection of many, many different diseases even though it has similar symptoms," says Brigitte Huber, a professor of pathology at Tufts University's Sackler School of Graduate Biomedical Sciences in Boston. She and others suspect that the retrovirus may be unleashing other underlying conditions and viruses in the body.
"This new retrovirus may be able, through infecting human cells, [to] induce a transcription of an endogenous virus," says Huber, who has been studying the presence of an ancient retrovirus (HERV-K18) dormant in most people but active in patients with CFS and multiple sclerosis. "We've already shown that Epstein-Barr virus can do exactly this."
Even in their testing for the XMRV retrovirus, Mikovits says, "We could see a human endogenous virus at the same time" as XMRV. "There are a number of old diseases that seem to be rising at an infectious rate," she says. Although this background noise of various viruses may be difficult to sort though, it brings clues to help researchers find the root cause of CFS. "It's possible, downstream, that this will all feed into the same mechanism," Huber says.
Even before the precise mechanisms are found, work toward finding treatment proceeds. Animal model testing is already underway, and Mikovits notes that her team is looking into some reverse transcriptase inhibitors that have already been approved by the U.S. Food and Drug Administration for other uses.
"Now we have a drug target and a marker," Mikovits says. "If we treat them with a drug and they get better, we win."
In the meantime, her team has been making quick strides toward a simple diagnostic test that doctors could use to check for the virus. Tests have been running smoothly in the lab, she notes, with some diagnostics companies already interested in the technology. She predicts a test will be available in less than six months. Mikovits adds that she is "excited that we will actually have some causes…rather than just building a better wheelchair."