Scientist using mircoscope

XMRV: A Small Virus Causes Large Controversy

XMRV Latest in String of Viruses NHF Has Monitored
Author: Sarah Aldridge

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 (discussed below).

Original Article:

A virus is causing consternation among researchers and patients. It’s called xenotropic murine leukemia virus-related virus, or XMRV. So far, two highly publicized studies have come to opposite conclusions. A 2009 study published in Science by Vincent C. Lombardi, PhD, a researcher at the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nevada, and colleagues, found evidence of the virus in 67% of patients with chronic fatigue syndrome (CFS) vs. 4% of healthy people.

However, a 2010 study published in the journal Retrovirology by William M. Switzer, MPH, and co-researchers at the Centers for Disease Control and Prevention (CDC), detected no XMRV in the CFS patients it studied. Because XMRV may infect many types of human cells, including blood cells, and can possibly be transmitted via blood products, the bleeding disorders community needs to stay abreast of the latest findings.

XMRV was first identified in 2006 in patients with prostate cancer. It is named for its relationship to murine leukemia viruses, which cause cancer in mice. Like HIV, XMRV is a retrovirus, storing its genetic material as ribonucleic acid (RNA), but then converting it to deoxyribonucleic acid (DNA), hijacking the cells’ machinery to produce more of the invading virus. Several retroviruses, called oncogenic retroviruses, have been linked with cancer. Others can cause immune deficiencies and inflammatory and neurological diseases. While some patients with CFS have elevated rates of prostate cancer, it is not clear if XMRV is the culprit.

Study Limitations

CDC estimates that up to 4 million people in the US have CFS. Symptoms include fatigue that does not improve with rest; joint, muscle and nerve pain; severe headaches; disrupted sleep; and cognitive issues. There is no cure, and patients are treated on a case-by-case basis.

The contradictory studies have been criticized for the following limitations: study size—each had 50 to 100 CFS patients; the way CFS patients were selected; and lack of standardized testing protocols. “The frequency of XMRV infection is still unknown,” wrote Steve Monroe, director of CDC’s Division of High-Consequence Pathogens and Pathology, in an e-mail interview with HemAware. More research is needed to determine the rate of XMRV infection in healthy people and in those with specific health conditions, he says. “An important next step will be to develop standardized testing methods that can be used by all XMRV researchers.”

The publication of a follow-up study by researchers at the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) in the Proceedings of the National Academy of Sciences has been postponed. It is expected to be released later this year. One of its authors is Harvey J. Alter, PhD, clinical studies chief of the Infectious Diseases and Immunogenetics section of the NIH’s Department of Transfusion Medicine. He helped identify the hepatitis C virus in 1988. “My colleagues and I are conducting additional experiments to ensure that the data are accurate and complete. Our goal is not speed, but scientific accuracy,” Alter said in a statement to The New York Times on July 14.

Information provided in a slideshow Alter presented on threats to blood safety in May at a meeting of the International Plasma Fractionation Association/Paul Ehrlich Institute in Zagreb, Croatia, supports the Lombardi study. In the presentation, Alter acknowledged:

  • The strength of the data
  • The probable transmission of XMRV to humans via blood
  • The association of XMRV with CFS, but without causality proven yet
  • That XMRV is in the donor blood supply at an early prevalence rate estimated at 3%–7%

Safety and Surveillance

Emerging viruses are a constant concern for government agencies, such as the CDC, that are involved in surveillance for blood-borne pathogens. In 2009, the US Department of Health and Human Services established the Blood XMRV Scientific Research Working Group to investigate methods of testing the virus and of determining its prevalence in people who donate blood or blood products. Currently, six labs—two at the FDA and one each at the Blood Systems Research Institute, CDC, National Cancer Institute, and Whittemore-Peterson Institute—are analyzing blood samples during a four-phase approach. All are pursuing the development of a standard assay, a test to detect the presence of the virus, which could be used to screen blood donors.

Organizations whose consumers use blood products, such as the National Hemophilia Foundation (NHF), also keep close tabs on blood safety. XMRV is simply the latest in a string of viruses NHF has monitored. “It reminds us of a time where there was another virus that we hadn’t identified that was labeled non-A, non-B hepatitis,” says NHF CEO Val D. Bias. Although that virus, later labeled hepatitis C, was discovered in the 1970s, it took 17 years to isolate it, he says. “So XMRV is a virus that could take us quite some time to isolate. But there’s no indication that we’ve seen yet that it’s of any particular harm to the blood supply.”

NHF has representatives on all the key blood safety committees of federal agencies in Washington, DC: Blood Products Advisory Committee, Advisory Committee on Blood Safety and Availability and the Transmissible Spongiform Encephalopathies Advisory Committee. Further, it has found strength in numbers, banding together with other patient groups that rely on blood products. “It’s so important for NHF’s leadership to support coalitions,” Bias says. “The American Plasma Users Coalition, A-PLUS, has expanded beyond just plasma users. We now have endorsements from both thalassemia and sickle-cell anemia patient organizations.”

So far, Australia, Canada, New Zealand and the UK have banned CFS patients from donating blood. In June, the American Association of Blood Banks, based in Bethesda, Maryland, released a bulletin recommending that its members discourage CFS patients from donating blood or blood products until more data is collected on XMRV. However, there is no current ban in the US.

There are several layers of protection used by blood banks and manufacturers of blood products to prevent viral contamination. “In the collection process, it’s the 60-day hold, it’s the questionnaire, it’s the patient registry—all help keep plasma pristine,” Bias says. Once the plasma is collected, different methods are used to inactivate viruses, including the use of heat and solvent detergent. Then it is fractionated, separated into the components used to make clotting factor and other blood products. (See “A Visit to a Plasma Collection Facility” in “Safe Journey,” HemAware January/February 2009, p. 64.)

“The effect of processed plasma inactivation on XMRV is currently unknown, although the current processes inactivate all evaluated retroviruses,” wrote Matthew Kuehnert, MD, director of CDC’s Office of Blood, Organ, and Other Tissue Safety, in an e-mail interview with HemAware. “At this time, there is no evidence to suggest that people with certain disorders should refrain from normal use of treatment and management options.”

Further, NHF issued a written statement in April 2010 that read, in part: “Thus, it is highly unlikely that this virus (XMRV) would pose a risk to users of clotting factor concentrates.” Patients are urged to contact their hematologist if they are concerned about the safety of their treatment products. NHF will continue to track the progress of research findings and keep the community informed.