Doubts Grow For Mouse Virus as Etiology of Chronic Fatigue Syndrome

Chronic Fatigue Syndrome (CFS) is estimated to affect 17 million individuals throughout the world. The exact cause of the disease is not known and there has been no effective treatment developed to date. CFS is characterized by overwhelming fatigue that is not improved with rest and can become worse with physical or mental exertion. In addition, patients often exhibit muscle weakness, muscle pain, impaired memory, impaired concentration, irritability, and insomnia. CFS is currently a diagnosis of exclusion, meaning that all other possible causes of the symptoms must be excluded before establishing a diagnosis of CFS. In addition, two criteria need to be met to make the diagnosis. The first is that the patient must have severe chronic fatigue for at least 6 months that is not relieved by rest and is not due to other medical or psychiatric condition characterized by fatigue. The second requirement is that the patient has at least four of the following symptoms: impairment of memory or concentration, chronic sore throat, tender neck or groin lymph nodes, muscle pain, joint pain, headache, unsatisfying sleep, or severe post- exercise fatigue. In 2009, a research paper published in the journal Science reported that a possible cause was found. This gave hope to CFS patients that a treatment could be developed. The researchers reported that they had identified DNA from a gammaretrovirus, xenotropic murine leukemia virus–related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls. It was concluded that “these findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS”. Both XMRV and HIV are retroviruses, and several antiretroviral medications used to treat HIV also showed activity against XMRV. Subsequently, many CFS patients were prescribed antiretroviral HIV medications in the hope that they would have some benefit. In addition, an advisory panel of the Food and Drug Administration recommended banning patients with CFS from donating blood in order to protect the country’s blood supply. Many research groups, including the Centers for Disease Control and Prevention, were not able to reproduce the finding that XMRV was found in the majority of CFS patients. This raised some doubt about whether XMRV was the cause of CFS. In the most recent issue of Science, two more papers provide additional evidence that XMRV is not the etiology of CFS. In the first paper, 61 patients with CFS were evaluated and none had evidence of the murine virus. In addition, XMRV DNA sequences were detected in commercial laboratory reagents. It was concluded that “evidence linking XMRV and … CFS is likely attributable to laboratory contamination”. In the second paper, human cell lines that produce XMRV were studied and the authors “conclude that XMRV… was generated by recombination of two proviruses” and that “the association of XMRV with human disease is due to contamination of human samples with virus originating from this recombination event”. The mounting evidence against XMRV as the cause of CFS caused Dr. Bruce Alberts, the Editor in Chief of Science, to write an editorial expression of concern regarding the results of the origin 2009 paper. In addition, Dr. Alberts has asked the original authors to retract their paper but they have stated that it was still premature to do so. Many CFS patients reacted with shock and anger regarding the new findings. More research needs to be done so that the exact cause of the disease can be identified and an effective treatment can be developed.