Chronic Fatigue and the Mysterious XMRV Link

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Everyone who suffers with this condition and the many thousands of practitioners involved in their health recovery are interested in whether there may be a causal agent identifiable through appropriate tests – not that there is a treatment on offer, but more a case of validation I suspect. This topic has attracted a great deal of attention in the orthodox and alternative medicine world and has some time to go before the explanations become viable treatments. Keeping up to speed with the science will assist all practitioners in their potential application.

The debate over XMRV began back in 2009 when researchers led by Judy Mikovits of the Whittemore Peterson Institute (WPI) for Neuro-Immune Disease in Reno, Nevada, reported in Science: traces of the virus in peripheral blood mononuclear cells, a type of white blood cell, of 67% of CFS patients. By contrast, only 3.4% of healthy controls were found to harbour the virus. The team also showed that XMRV could infect human cells and concluded that the virus—which had previously been linked to prostate cancer—might play a role in causing CFS.

See previous post here

This was then challenged and I reported on this in a subsequent posting here.

The Proceeding of the National Academy of Science (PNAS) has now published the latest paper exploring this link after holding it for review for 2 months.[1] Headed up by well known viral seeker – Harvey Alter working at the National Institute of health and the US FDA they reviewed 37 CFS patients.

The samples had been collected back in the 1990’s by a Harvard specialist and 32 (87%) of these samples showed evidence of the virus, whilst a comparable healthy group showed just 3 out of 44 (6.8%).

Most scientists remain cautious despite the obvious excellent experience of the lead scientist, in part this is because retroviruses (Retroviruses are an important group of pathogens that cause a variety of diseases in humans and animals) have previously been linked to conditions that do not after time prove to be correct.[2]

The slight fly in the ointment in this paper is that the scientists did not exactly replicate the original study design. XMRV is a so-called xenotropic murine virus, which means it can no longer enter mouse cells but can infect cells of other species. (Murine means “from mice.”) The researchers in the PNAS paper say the viral sequences they find are more diverse than that and resemble more closely the so-called polytropic viruses, which is why they adopted the term MLV-related virus, for murine leukemia virus.

This means the study found another virus albeit that the genetic material closely resembles XMRV and likely reflects the same pattern of viral infection as described by Mikovits.

The authors state:

Even if subsequent studies confirm an association between MLV-like viruses and CFS, that will not establish a causal role for these viruses in the pathogenesis of this illness. For example, such a high frequency of infections with MLV related viruses in patients with CFS could reflect an increased susceptibility to viral infections due to an underlying CFS-related immune dysfunction, rather than a primary role for these viruses in the pathogenesis of CFS.


One of the questions on everyone’s mind is why do some labs seem to find it and others do not – maybe this is down to handling techniques rather than geography as was first postulated – hopefully the relevant teams will get this aspect cleared up in the coming months. The next issue of course is what does one do about it if your patient is at some time in the future tested as positive – Indications are that maintaining a competent immune capacity is a key element of prevention – but as for resolution, more work will need to be done.


[1] Shyh-Ching Lo, Natalia Pripuzova, Bingjie Li, Anthony L. Komaroff, Guo-Chiuan Hung, Richard Wang, and Harvey J. Alter Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors PNAS 2010 : 1006901107v1-201006901. View Full Paper

[2] Voisset C, Weiss RA, Griffiths DJ. Human RNA “rumor” viruses: the search for novel human retroviruses in chronic disease. Microbiol Mol Biol Rev. 2008 Mar;72(1):157-96, table of contents. View Full Paper

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  • Thanks for posting this Mike. I think you hit the nail on the head with pointing out how important validation is for people experienceing ME/CFS. Hopefully, at the very least, this will turn out to be a good biomarker for the illness if nothing else.

    Just want to stress that MLV’s are also retrovirues too. Lo, one of the study’s main authors, has pointed out that these are close “cousins” of XMRV and, in a way, its “good” that they shown up as now you have a retrovirus behaving like a retrovirus i.e.genetic variablity is showing which is what happens to retroviruses naturally over time. Alter, the other main author also points out that this variation is what you often see in other viral infections like Hepatitis C.

    One thing that has been pointed out with both the “positive” studies is that they had excellent patient cohorts, usually conforming to the strict Canadian Consenus Criteria. (CCC) as well as Fukuda. The big problem with ME/CFS is that it is such a heterogenous population you need very tight criteria to identify the neurlogical ME/CFS base, as defined by WHO G93.3 which the CCC does. That’s not to say other groups of patients aren’t organically sick too but they may well have different aeitologies. With criteria weaker than the CCC it’s very very easy (as demonstrated by Prof L Jason et al) to select people who have other diagnoses like depression, burnout etc etc. This will then obviously skew the data and results. For instance the recently published CDC study that found no XMRV/MLV patients were selected by phone interview and many had never had a physician diagnosis of ME/CFS. Rather worrying way to conduct a trial!

    Personally I don’t think there will ever be “one cause” for ME/CFS even with those who fit the CCC – but there is a possibility that XMRV/MLV may be a significant sub group, possibly reflecting the more severely ill.

    I do think its imporant for practioners to be aware that when a patient presents with “fatigue”, “chronic fatigue”, “ME”,”CFS” that this could be anything from a quite severe neurological illness that can be very tricky to sort out and treat, right through to something much more easily treatable like Adrenal Fatigue, allergies, poor diet etc. (though all these can be complicating factors in the most seriously ill too!).

    Thanks for posting this, and it will be interesting to see where the story goes from here……Any seminars planned on the treatment of retroviral illness with nutrition?! Andrew


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