People with the condition are much more likely than others to harbor a little-known pathogen. The long, fruitless search for the cause of chronic fatigue syndrome has taken a curious turn. Scientists report online October 8 in Science that an obscure retrovirus shows up in two-thirds of people diagnosed with the condition. The researchers also show the retrovirus can infect human immune cells.
These findings don’t establish that the pathogen, called gammaretrovirus XMRV, causes chronic fatigue, cautions study coauthor Robert Silverman, a molecular biologist at the Lerner Research Institute of the Cleveland Clinic. “Nevertheless, it’s exciting because it is a viable candidate for a cause.”
Roughly 1 to 4 million people in the United States have chronic fatigue syndrome, according to the Centers for Disease Control and Prevention. The condition shows up as mental and physical exhaustion, memory lapses, muscle pain, insomnia, digestive distress and other health problems. Doctors often diagnose chronic fatigue only after ruling out everything else. Its cause is unknown.
In the new study, the researchers tested blood from 101 people with chronic fatigue syndrome and found that 68 were infected with XMRV. When the scientists analyzed blood from 218 healthy people as a control group, only eight had the virus — 4 percent. The study participants lived in various parts of the United States.
“This is a very striking association — two-thirds of the patients,” says John Coffin, a virologist at Tufts University in Boston who wasn’t involved in the study. A 4 percent infection rate in the healthy controls is also substantial, he notes, because it suggests that 10 million people in the United States are harboring this hidden infection.
If the retrovirus indeed is found to cause chronic fatigue, the infected 4 percent in the control group might represent people who have been infected for a short time and haven’t developed symptoms, or who have kept the virus in check, says study coauthor Judy Mikovits, a cell biologist at Whittemore Peterson Institute in Reno and at the University of Nevada, Reno.
Based on its genetic makeup, XMRV arose from a mouse retrovirus that somehow jumped to humans.
Mikovits asserts that the retroviral infection might result in an immune deficiency that leads to chronic fatigue symptoms. Retroviruses are known to attack the immune system, with HIV being the best-known example. In this study, researchers showed that XMRV infected immune cells in the blood.
“This may end the controversy as to whether there is an underlying infection in some cases of chronic fatigue syndrome, but is unlikely to explain all cases,” says internist Dedra Buchwald of the University of Washington in Seattle. Retroviruses can awaken latent viruses already in cells. It is possible that chronic fatigue symptoms are caused not by XMRV but by other viruses that it activates, she says.
Meanwhile, retroviruses harbor pro-growth genes, and some cause the blood cancer leukemia in animals and people. XMRV — or xenotropic murine-leukemia-virus–related virus — itself shows up in some men with prostate cancer, particularly those with aggressive malignancies, another research team reported last month in the Proceedings of the National Academy of Sciences.
Gammaretroviruses, a subset of retroviruses, also cause disease in gibbons, cats and koalas, Silverman says. “XMRV is the first member of this genus of retrovirus to be found in humans,” he notes.
In the new study, the researchers also found hints that the retrovirus is transmitted by blood, as are some other viruses, including HIV. But it’s probably not spreading very fast, because people with chronic fatigue “are too sick to do anything,” Mikovits says.
Further research is under way to fine-tune testing for the retrovirus, and more blood analyses are planned that will clarify its occurrence rate in the general population. Mikovits and her colleagues are investigating already-approved antiretroviral drugs to see if these will benefit people who have chronic fatigue.