Xenotropic murine-related retrovirus (XMRV)

This retrovirus was reported to be associated with CFS last October in a study published in the prestigious journal Science. In order to get published, the scientists involved had to a run a number of further studies to satisfy the reviewers of the article. In Dr. Komaroff’s opinion the study was “pretty impressive.”

The study found the nucleic acid, the RNA of the virus, or the DNA after it enters the human genes, in 67% of patients as opposed to 4% of control subjects—68 of 101 CFS patients vs. 8 of 218 controls. The p-value was <0.001, meaning the result was highly statistically significant.

Next, the study found the protein of the virus in 63% of patients (19 of 30) compared with none of the healthy controls (0 of 16) ( p < .00001).

Furthermore, the researchers said they found the actual virus not only in the cells, but also freely floating in the plasma (that is in the blood—both in the fluid and in the blood cells). From the small number of patients tested, 83% (10 of 12 patients) had the virus in the plasma; while none of the controls (0 of 12 controls) had the virus detected (p<.00003).

Finally, the researchers found that patients with CFS illness were making antibodies to this virus in 50% of the small number of patients given this test, and in none of the healthy controls that were tested—9 of 18 patients vs. 0 of 7 controls (p<.02).

Dr. Komaroff stated, “that’s a reasonably impressive set of numbers, but it is not a perfect study, as the authors of the study would readily admit—one would have liked to have all of the tests done on all of the larger number of patients and controls.”  However, no study is a perfect study—and the question arises, can this study be replicated by other researchers around the world?

Other groups have attempted to repeat the first element of the Science study (Lombardi, et al., Science 2009; 326:585), i.e., the presence of viral nucleic acid in CFS patients vs. controls. However, none of the three European groups tested for (or have not published results of) the latter three elements of the Science study: viral protein, presence of the virus itself in the blood, and viral antibodies in the serum.

This is an important deficiency in the European studies. However, all three European studies failed to find viral nucleic acid of XMRV in any of the patients and controls.

So at the moment there is a provisional judgment among many infectious disease experts that there could have been something wrong with the original study. Dr. Komaroff’s judgment on the three papers that failed to confirm the results of the first study “…is that although they were done by very skilled people, and were solid work in many respects—there was one problem with all of these papers that could have undermined their ability to find what they were looking for, that is, the viral nucleic acid.” 

In his opinion, the “dust has not yet settled on this controversy, and we still don’t know if this retrovirus is associated with CFS.”

What if it were shown that this virus is associated with CFS?

Any statistically significant association of the XMRV virus and CFS would be an important finding, but the finding itself would lead to more questions. (As already stated, any association between the virus and CFS has yet to be confirmed.)

A significant association could mean two things: a) that the virus is a cause of CFS, either acting alone or in combination with other viruses living within us; or b) that this virus is actually pretty common in most people, but in most people the viral load (the actual number of viruses) is very low, so it’s hard to pick-up in tests we have today.

However, in CFS something could go wrong with the immune system, and the XMRV virus, that is usually asleep, gets awakened by the immune dysfunction—but it’s not itself a cause of the illness. It could be a resulting factor, not a primary factor—that is, a reflection of the illness, not a cause.

If XMRV is determined to be associated with CFS, then there are ways to further determine if the virus is causal in the illness—the most obvious of which is to use medication that at least in the test tube kills the virus. If this kind of medication led to lower virus levels in the body, and to patients feeling substantially better, that would be pretty good evidence that XMRV is a cause.

Although Dr. Komaroff would like for there to be a microbe that is a single cause of the illness— since that would simplify everyone’s work in finding a treatment, “he has never believed it will be that simple” —we already know (as discussed above) that several agents can trigger the illness. Maybe XMRV will be one of them, either a common or uncommon a cause.

[2015 Editorial note: By 2012 it was definitively established that all the positive results involving XMRV were the result of contamination of the samples examined in labs that also had mice. It was further shown that the virus does not infect humans. So there is no tie between XMRV and CFS.]