XMRV Update

New study links chronic fatigue syndrome and XMRV virus family

Update: On May 31, 2011, the journal Science published two papers online that it says cast doubt on the link between XMRV and chronic fatigue syndrome (CFS). The journal also published an "Editorial Expression of Concern," stating that any association between XMRV and CFS was likely due to lab contamination. Science editors have asked researchers to voluntarily retract their 2009 paper linking XMRV and CFS.

Original Article:

A much-anticipated study on xenotropic murine leukemia virus-related virus (XMRV) reports a link between chronic fatigue syndrome and a family of viruses called murine leukemia virus (MLV)-related viruses, which includes XMRV.

Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors,” by Shyh-Ching Lo, MD, PhD, Harvey J. Alter, PhD, and co-authors, was published in the online Proceedings of the National Academy of Sciences (PNAS) on August 23, 2010. The study had been held up for further investigation after its initial findings refuted a study by the US Centers for Disease Control and Prevention, which showed no association between chronic fatigue syndrome (CFS) and XMRV.

Chronic fatigue syndrome is characterized by fatigue; pain in the joints, muscles and nerves; severe headaches; disrupted sleep; and cognitive issues. One of the conclusions drawn by the researchers who published the study in the 2009 Science article was "patients with CFS have an elevated incidence of cancer." The cause has not been determined. Up to 4 million people in the US have CFS. There is no cure.

The delay in publication provided more time to bolster the data, say the researchers from the US Food and Drug Administration’s Center for Biologics Evaluation and Research, the Department of Transfusion Medicine at the National Institutes of Health, and Harvard Medical School. Although the investigators found no evidence of XMRV in the study subjects, they did discover MLV-related virus in the samples they sequenced. Further, the researchers said that the term “MLV-related virus” is more comprehensive, incorporating XMRV and other viruses from the same family of retroviruses. Retroviruses store their genetic material as ribonucleic acid (RNA), but convert it to deoxyribonucleic acid (DNA), overtaking the cell’s machinery to manufacture more of the virus.

The researchers took blood and DNA samples from CFS patients and volunteer blood donors, who served as controls. Of the 37 CFS patients examined, 32 (86.5%) showed evidence of four different MLV-like virus gene sequences, compared with three of the 44 controls (6.8%). The authors concluded, “Although we find evidence of a broader group of MLV-related viruses, rather than just XMRV, in patients with CFS and healthy blood donors, our results clearly support the central argument by Lombardi et al (published in Science in 2009) that MLV-related viruses are associated with CFS and are present in some blood donors.”

The major differences between this study and the CDC’s were:

  • The strong association between CFS and MLV-related virus
  • The degree to which the virus was found in healthy donors
  • The genetically diverse group of MLV-related viruses detected versus the near genetic identity of XMRVs

However, the authors stressed that their findings indicate association, not causation. It is still not known if the virus plays a primary role in causing CFS or if CFS weakens the immune system, allowing opportunistic viruses to invade the body.

Further research is needed to determine if the strong association between CFS and MLV-related viruses is found in other groups of CFS patients or in patients with co-morbidities, such as HIV or hepatitis C. Studies are under way at the National Heart, Lung, and Blood Institute to develop standardized tests to detect MLV-related viruses in the blood. So far, three HIV drugs have shown promise inhibiting XMRV in the lab.

Further, a working group of government agencies is examining the blood supply for MLV-related viruses. Larger studies of blood donors are needed to ascertain whether the virus is transmissible through blood. To date, there is no evidence that the viruses have been spread through blood donations or that people using blood products are at risk. The National Hemophilia Foundation is staying abreast of the latest developments concerning XMRV and MLV and will keep patients informed.