Issue: November 2009

Does a Virus Cause Chronic Fatigue?

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by Ker Than

Suppose you suffered from a disease that caused severe pain and headaches, left you feeling exhausted all the time, and played tricks with your memory? That is pretty much the description of the symptoms of chronic fatigue syndrome (CFS), a condition affecting an estimated 1 million people in the U.S., many of them women between the ages of 30 and 50. Of course, even healthy people feel tired occasionally, or have a headache or a spell of forgetfulness, but CFS is a lot worse. However, because a physical cause for the condition had not been identified, some doctors and researchers have been inclined to question its existence, or at least have suggested that it might be a psychiatric disorder. Treatments have focused on behavioral approaches aimed at helping patients cope. But in a study just published in Science, CFS has been linked to a particular virus — a finding that, if it is replicated and supported by other research, will presumably put such doubts to rest.

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Chronic Fatigue Syndrome is a debilitating medical condition affecting an estimated 1 million people in the U.S., many of them women between the ages of 30 and 50. Persistent exhaustion and malaise is accompanied by severe joint and muscle pain, migraine headaches, and short-term memory loss.

In the new study, published in the October 9 issue of SciencExpress (the online portal for Science), researchers tested the blood of 101 patients with CFS and found the virus, xenotropic murine leukemia virus, or XMRV, in two-thirds of them. This is a virus that, while not well-known, had previously been linked to prostate cancer. In another potentially troubling finding, the team found XMRV in 8 of 218 healthy individuals, or roughly 4% of them.

If these figures are borne out in larger studies, the scientists say, it means that perhaps 10 million people in the U. S. and hundreds of millions worldwide are infected with a virus with a possibly significant potential for causing disease. "Any virus at that level is obviously cause for concern," Stuart Le Grice, a researcher at the National Cancer Institute who was not involved in the study, told the New York Times.

A Retrovirus like HIV

XMRV is a so-called retrovirus. This means it is like HIV, the virus that causes AIDS. Retroviruses have genetic material made of RNA, which they translate into DNA and embed into the DNA of their host cells.

XMRV's link to prostate cancer was first reported three years ago, after the virus was discovered in a few prostate cancer patients; more recent observations have found XMRV in nearly a quarter of biopsies testing positive for prostate cancer.

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XMRV is a retrovirus. Retroviruses have genetic material made of RNA, which they translate into DNA and embed into the DNA of their host cells. ABOVE: An artist's conception of a retrovirus in the human body. BELOW: XMRV, first linked to prostate cancer in 2006, has now been found in the white blood cells of CFS patients.

Whittemore Peterson Institute

In the new study, the scientists used a molecular biology technique called Western blotting to determine that XMRV specifically infects white blood cells called lymphocytes in CFS patients. In the Western blot, scientists first separate the different cells in a blood sample and then "probe" them with antibodies. Antibodies, you may recall, are Y-shaped molecules produced by the immune system that bind to foreign objects and pathogens in the bloodstream and either neutralize them or mark them for later destruction by specialized white blood cells. In this case, the scientists used animal antibodies that were known to bind to human XMRV to probe the CFS patients' blood samples. When they did this, the antibodies aggregated around lymphocytes, indicating that those cells were infected with XMRV.

Additionally, the team compared the genetic codes of the CFS and prostate cancer strains of XMRV and found that they are more than 99 percent identical to each other. The two strains are only 90 percent identical to MRV (murine leukemia virus), a related retrovirus that affects only laboratory mice. This suggests that the CFS and prostate cancer XMRV strains may have a common origin, but did not jump to humans from lab mice, the scientists say.

The team also demonstrated that XMRV is infectious. They did this by co-culturing XMRV-infected blood cells from CFS patients alongside healthy prostate cells. When they analyzed the prostate cells later, the cells were infected with XMRV. It is still not known how XMRV is transmitted, but since the virus is found in CFS patients' blood samples, it may be transmitted through blood or other bodily fluids such as saliva.

Not an Air-Tight Case

The authors of the new study stress that their findings are not proof that XMRV causes CFS. It's possible, for example, that XMRV is a so-called passenger virus that catches a ride in patients whose immune systems are already weakened by other diseases. The researchers point out, however, that if XMRV does cause CFS, that would explain many aspects of the disorder. For example, people with CFS often complain of neurological problems, show higher incidences of cancer and exhibit immune system problems. The new study shows that XMRV infects immune system cells, and other retroviruses, such as MLV in mice and HIV in humans, have been associated with cancer and nervous system problems.

"The presence of infectious XMRV in lymphocytes may account for some of these observations of altered immune responsiveness and neurological function in CFS patients," the authors write.

Potential Treatments

While more research is needed to confirm the link between XMRV and CFS, the new finding raises the possibility that CFS sufferers could benefit from drugs similar to the ones designed to fight AIDS. "You can imagine a number of combination therapies that could be quite effective and could at least be used in clinical trials right away," study leader Judy Mikovits, the research director at the Whittemore Peterson Institute in Reno, Nevada, told Reuters.

Mikovits told Science that her team's study "proves beyond a shadow of a doubt that CFS is a real disease." But some of her colleagues are not so sure. The findings were met with skepticism by William Reeves, director of CFS research at the Centers for Disease Control and Prevention. Reeves told the New York Times that the authors failed to specify age or gender for their patients and controls, or indicate how long they had been ill.

"If I don't know the nature of the cases and controls, I can't interpret the findings," Reeves said. "We and others are looking at our own specimens and trying to confirm it," he said, adding, "If we validate it, great. My expectation is that we will not."

In an interview with the New York Times, John Coffin, a molecular biologist at Tufts University in Massachusetts who also did not participate in the research, suggested looking at stored blood samples of CFS patients to find out if there were people who became ill a certain amount of time after contracting XMRV. If antiviral drugs make patients improve, that will also help make the case for a link between the virus and CFS, Coffin said.

Discussion Questions

Why do you think Mikovits feels that her team's research proves that CFS is a "real disease?" What criteria are implicit in that statement? What further steps would you take to prove (or disprove) the XMRV-CFS link?

Journal Abstracts and Articles

(Researchers' own descriptions of their work, summary or full-text, on scientific journal websites).

"Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome." www.ncbi.nlm.nih.gov/ pubmed/ 19815723? ordinalpos= 1&itool= EntrezSystem2. PEntrez. Pubmed. Pubmed_ResultsPanel. Pubmed_DefaultReportPanel. Pubmed_RVDocSum.

Bibliography

Coffin, John M. and Jonathan P. Stoye. "A New Virus for Old Diseases?" SciencExpress (October 9, 2009) [accessed November 5, 2009]: www.sciencemag.org/ cgi/ content/ short/ 1181349.

Lombardi, V.C., Judy A. Mikovits et al. "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome." SciencExpress (October 9, 2009) [accessed November 5, 2009]: www.ncbi.nlm.nih.gov/ pubmed/ 19815723? ordinalpos= 1&itool= EntrezSystem2. PEntrez. Pubmed. Pubmed_ResultsPanel. Pubmed_DefaultReportPanel.Pubmed_RVDocSum.

Grady, Denise. "Is a Virus the Cause of Fatigue Syndrome?" New York Times. October 12, 2009. [ accessed November 3, 2009]: www.nytimes.com/ 2009/ 10/ 13/ health/ 13fatigue.html?_r= 1&pagewanted= all].

Keywords

chronic fatigue syndrome, CFS, retrovirus, xenotropic murine leukemia virus, XMRV, prostate cancer, Judy A. Mikovits, Whittemore Peterson Institute