XMRV: The Puppet Master?

Dr. Bell speculates that XMRV could be a kind of ‘puppet master’ that allows other infections such as EBV or HHV6 or Lyme or enterovirus to  become exacerbated.  Dr. Coffin echoed this idea in his article “A New Virus For Old Diseases”.

Dr. Huber, a researcher studying endogenous viral elements in ME/CFS has suggested that XMRV could unlock endogenous retroviral elements in our DNA.  Dr. Cheney stated that based on the limited results from his clinic it could XMRV could be a factor in autism and ADHD and wonders about arthrits, asthma and cancer.  Dr. Mikovits has reported that XMRV can be found in autism and ‘atypical MS’ patients. It’s all a bit overwhelming.


The Nevada Autism Commission revealed that 40% of a ‘small group of children’  with autism tested postive for XMRV.  Dr. Mikovits verified this stating, “we have actually done some of these studies (in ASD children) and found the virus in a significant number of samples that we have tested for.

It could be linked to a number of neuro-immune diseases, including autism” but that at best it would be one  several factor that contributed to the disorder.  Dr. Mikovits also speculated that the virus could be a factor in  vaccination triggered autism (see below).

Infectious mononucleosis

No one’s mentioned a key factor in many patients journey  – infectious mononucleosis.   Could an XMRV infection be a risk factor for getting infectious mononucleosis; ie. do people who get the more severe form of Epstein-Barr virus infection (infectious mononucleosis) rather than the  less severe form (mild cold)  tend to carry the XMRV virus?

The Dubbo and  Taylor studies could show that XMRV is not restricted to the ME/CFS patients. It turns out that if you have infectious mononucleosis you also have an increased risk of coming down with multiple sclerosis and the WPI has already reported finding XMRV in ‘atypical’ MS patients. Could the scenario go :-XMRV infection in childhood = increased risk of infectious mononucleosis = increased risk of ME/CFS or multiple sclerosis?

Other diseases

ME/CFS is not the only disease with disabling fatigue, cognition problems, sleep problems, etc. Besides related diseases like fibromyalgia there are also a number of diseases which don’t appear to be related to chronic fatigue syndrome at all but which have subsets of patients who look very much like chronic fatigue syndrome patients.

A significant subset of post-cancer patients, post ICU patients, post heart surgery patients, patients with liver disease and multiple sclerosis patients have a very CFS-like condition. Researchers have speculated that they are in fact chronic fatigue syndrome showing up in other diseases.

What these conditions share is a stress trigger; whether it comes in the form of an infection, a physical trauma (fibromyalgia), cancer treatment, surgery, etc.  This, of course that the stress response plays a critical role in the development of this illness. Note that this does not at all conflict with any of the statements that Dr. Mikovits has made regarding possible triggers for XMRV activation; two of them she mentioned – cortisol and inflammatory cytokine levels  – are increased during the stress response.

Could the CFS-like post-cancer, post-ICU,  MS patients, etc. patients be harboring the XMRV virus? The possibilites for this virus – at this very early stage when we don’t know much – appear to go on and on.

Why might retroviruses at least theoretically be able to trigger so much disturbance?  Because we’re pretty much stuck with them; instead of eventually getting killed off in the body like other viruses they tend to linger in the body  – i.e. they are chronic – and  they can be pretty good (aka HIV) at creating a condition which other pathogens can take advantage of.

Let’s not forget , though, that most retroviruses are completely harmless.. In fact our DNA is studded with the remnants of old retroviruses that have embedded themselves in our genome.

Dissenting views

There is also some reason to believe that this virus might not be some sort of ‘Puppet Master’ that turns on a ‘viral cascade’ in patients. A study by Dr. Nicholson found tthat one virus does not appear to open the door to another virus in ME/CFS patients.  Dr. Natelson reports finding very, very few viruses in the patients that he sees.

Reports from the WPI, on the other hand, mention finding dozens of  different types of viral fragments in the sophisticated tests in chronic fatigue syndrome patients and very few in controls. Is technology the difference here? Or are these physicians looking at different types of patients? Clearly we’re still in the early stages of getting a clear picture of the viral component in this disorder.

Triggering factors

Since we’ve seen that healthy people can carry this virus it’s clear that XMRV doesn’t necessarily cause disease. If it does turn out to be a key factor in chronic fatigue syndrome and other neuro- immune illnesses something’s going to have to either turn it on or exacerbate its effects when it is active. What could turn XMRV from a rather innocuous bystander into a big problem?


Dr. Mikovits has speculated that stress hormones like our friend cortisol, or inflammatory cytokines or vaccines could all concievably shift XMRV from a Dr. Hyde to a Dr. Jekyll-like state.  Many studies have shown that low levels of cortisol are present in a significant portion of  ME/CFS patients. (Dr. Holtorf argues that the most widely used cortisol tests under estimate the true prevalence of low cortisol in this disorder).  Chronically low cortisol produces inflammation (immune activation) which Dr. Mikovits suggests could trigger XMRV replication.

Inflammatory cytokines

The Dubbo studies suggest that cytokines are a triggering factor in chronic fatigue syndrome. These studies tried to determine how an infection turned into chronic fatigue syndrome. They found that people who had high inflammatory cytokine levels early in their illness tended to get chronic fatigue syndrome. Those people who didn’t have the high inflammatory cytokine levels tended to recover.

Two prospective studies – the Dubbo studies and Renee Taylors recent study – have followed people as they came down with ME/CFS following an infection. Both presumably have blood samples they can test.  These studies show that about 10% of infectious mononucleosis patients come down with postviral fatigue and a smaller percentage come down with chronic fatigue syndrome. Hopefully they are now testing  their samples to see if the virus was restricted to the patients who later became ill with chronic fatigue syndrome.


Given  the virus’s propensity for T and B cells it sounds like any kind of immune activation could – by causing T and B cells to replicate – resulting in increased replication of the virus and indeed Dr. Mikovits speculated that XMRV infection could play a role in the sometimes negative effects seen in vaccinations. (Annette Whittemore explained the WPI is not not advocating vaccine use in children. “We certainly are advocating vaccinations and how important those are to the well being of children”.)


Intriguingly given the preliminary evidence by Dr. Baraniuk that amyloidosis may play a role in chronic fatigue syndrome (ME/CFS) a 2009 study finding that ‘amyloidgenic fragments’ (SEVI) in prostate tissues appeared to ‘greatly increase’ XMRV infection. The authors noted that these fragments appeared to to create “an environment that provides a natural enhancer of (XMRV) infection.”

Because there are several different types of amyloidic proteins a connection to Dr. Baraniuk’s work is not clear. But because the virus can be carried in otherwise healthy people researchers will be looking for a ‘triggering’ factor that potentiates it. Could amyloid fragments in ME/CFS patients central nervous system be a contributing factor?

All is speculation at this point but should this virus turnout to play a major role in this disorder finding a ‘triggering factor’ will loom large particularly with regard to disease prevention. Retroviruses generally cannot be eliminated from the body but 30 years of HIV research has shown that can be controlled.

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