By NCF Medical Committee©2009

From Winter 2009-2010 Forum

By now, many patients have heard of the findings of a new retrovirus in CFS. A research paper, recently published in journal Science, titled "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome" disclosed new research results linking XMRV and CFS [1]. The last time a retroviral link garnished major attention was the 90's research by Elaine DeFreitas, Ph.D. at Wistar in Philadelphia [2].

What is XMRV?

XMRV, short-hand notation for Xenotropic Murine Leukemia Virus-related virus, is formally categorized byscientists as a gammaretrovirus. It is a member of the retroviridae family which, in this case, has been associated with leukemias and sarcomas.

Why is it important?

Judy Mikovits, Ph.D., along with colleagues at the Whittemore Peterson Institute for Neuro-Immmune Disease (WPI), the National Cancer Institute as well as The Cleveland Clinic, have identified an association between XMRV and CFS [1]. Using blood samples, the XMRV gag protein was detected in 67% of the 101 patient samples while it was present in 3.7% of the 218 control samples. Subsequently, Robert Silverman,Ph.D. from the Cleveland Clinic detected XMRV env and gag proteins in 7 out of 11 samples provided by the WPI. Certainly, this discovery provides additional research clues to the CFS puzzle. Furthermore, what is intriguing is that XMRV has been recently identified in 23% of prostate cancers [3]. This may serve to bolster the evidence of a link between CFS and cancer.

How is XMRV transmitted?

According to WPI's website, XMRV is thought to be transmitted through body fluids such as blood, semen, and mother's breast milk but is not transmitted through the air. It is not known whether XMRV is more easilytransmitted than other human retroviruses.

Has XMRV been found in other illnesses?

In a recent interview, Dr. Judy Mikovits stated that they also found XMRV in people with autism, atypical multiple sclerosis and fibromyalgia [4]. As such, XMRV would appear to not be an exclusive marker for CFS.According to the Cleveland Clinic, "This finding shows there is an association between XMRV and CFS but does not prove that XMRV causes CFS" [5].

Is there much in the medical literature about XMRV?

A search in the National Library of Medicine yielded 17 papers on XMRV; a search of the U.S. Patentdatabase yielded zero patents; and a search of the World Patent database yielded one patent issued to Silverman et. al. on a gammaretrovirus associated with cancer (prostate) [6].

Are there any treatments for XMRV infections?

Though there haven't been many comments thus far regarding potential treatments, antiretroviral drugs may prove to be applicable.

Is XMRV related to the HTLV-II like virus discovered by Elaine DeFreitas, Ph.D.?

XMRV is a gammaretrovirus while HTLV-II is a deltaretrovirus. These classifications of retroviruses makes them distinct and different. Nucleotide sequences for both of these viruses would have to be examined in detail to see if there was any homology between them [2,7].

Is XMRV related to the JHK retrovirus found in CFS patients and discovered by Sidney Grossberg, M.D.?

According to Dr. Grossberg's website, "the JHK virus is an enveloped, relatively fragile particle containing RNA, reverse transcriptase, and prominent, knobbed glycoprotein projections. Although the JHK virus resembles a retrovirus (but 35% smaller than most other retroviruses), it is clearly not like any of the known human retroviruses as determined either by polymerase chain reactions or electron microscopy. The JHK-3 B-lymphoblastoid cell line that constitutively produces the JHK virus (and the Epstein-Barr virus as well) has the antigenic markers of immature B-lymphocytes by flow cytometry. cDNA libraries produced by reverse transcription of JHK viral RNA have been constructed and are being analyzed; the sequences determined of the many clones produced have so far revealed no significant homology with known viruses. The possible etiological role of the JHK virus in diseases that may involve B-lymphocytes, such as leukemia, lymphoma, chronic fatigue syndrome or immuno-dysfunctional states, remains to be determined [8,9,10]." It would appear that the JHK virus differs from XMRV judging by Grossberg's information.

Does XMRV fit the epidemiology profile for CFS?

A 1991 paper by David Bell, M.D. on a cluster of pediatric cases may shed light as to whether or not XMRV fits the epidemiologic profile for the disease [7]. This paper provides information on the Lyndonville outbreak. The risk factors, found to be statistically significant, identified to be associated with CFS were raw milk and raw eggs; exposure to dogs in the house and cats on the property; hot air heating source; and appendicitis. Unless proven otherwise, the NCF's medical committee does not believe that XMRV fits this particular epidemiologic profile.

Do you suggest that patients get tested for XMRV?

The NCF believes that this is a decision that must be made by patients themselves.

In closing, the publicity and attention that scientific discoveries bring to this disease are welcome. Increased awareness and visibility adds to the knowledgebase as to what patients must face in their day to day struggles with the illness. The XMRV discovery serves to add new evidence as to the serious nature of this disease.

References:

1. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome; Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH,Mikovits JA; Science. 2009 Oct 23;326(5952):585-9.
2. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome; DeFreitas E, Hilliard B, Cheney PR, Bell DS, Kiggundu E, Sankey D, Wroblewska Z, Palladino M, Woodward JP, Koprowski H; Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2922-6.
3. XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors; Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR; Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16351-6.
4. Cancer-Causing Virus Linked to Chronic Fatigue; AMY DOCKSER MARCUS; Wall Street Journal; Oct 12, 2009; http://online.wsj.com/article/SB125501227713473525.html
5. Research shows a potential retroviral link between XMRV and Chronic Fatigue Syndrome; Cleveland Clinic News; 10/08/2009; http://my.clevelandclinic.org/news/2009/research_showing_potential_retroviral_link_between_xmrv_and_cfs.aspx
6. Gammaretrovirus associated with cancer; World Patent # WO/2006/110589 issued on 10/19/06; Inventors: Silverman R, Klein EA, Derisi J, Ganem D, Casey G; Applicants: Cleveland Clinic Foundation and the University of California
7. Method and compositions for diagnosing and treating chronic fatigue immunodysfunction syndrome; World Patent #WO92/05760 issued 04/16/92; Inventors: DeFreitas E and Hilliard B; Applicant: Wistar Institute
8. Sidney E. Grossberg, M.D.; www.mcw.edu/microbiology/SidneyGrossberg.htm
9. A human B-lymphoblastoid cell line constitutively producing Epstein-Barr herpesvirus and JHK retrovirus; Grossberg SE, Kushnaryov VM, Cashdollar LW, Raisch KP, Miller G, Sun HY; Res Virol. 1997 May-Jun;148(3):191-206
10. Human virus associated with chronic fatigue immune deficiency syndrome and assay therefore; US Patent #5,827,750 issued 10/27/98; Inventors: Grossberg SE, Kushnaryov VM, Cashdollar LW, Carrigan DR, Knox KK; Assignee: Medical College of Wisconsin
11. Risk factors associated with chronic fatigue syndrome in a cluster of pediatric cases; Bell KM, Cookfair D, Bell DS, Reese P, Cooper L; Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S32-8.