Journal of Infectious Diseases Reports on the Status of XMRV Research

As those of you who follow developments in the progress of research into the recently discovered retrovirus XMRV and human disease are aware, lately there has been a great deal of confusion about what the correlation is if any.  The original Lombardi et al paper that came out of the Whittemore Peterson Institute, and was published in the journal Science, made a strong case that XMRV is associated with human disease. Several follow up studies did not corroborate this finding, but have numerous methodological errors and serious conflicts of interest.  Much of the confusion in the mainstream media seems to have arisen because they received PR announcements when these studies were published (after a delay), but did not do research to understand what has transpired during the delay nor to establish the context of these studies, and they are unaware of the Harvard/NIH study that supports the original WPI findings.  As a result, there has been widespread dismissal of the original research as being nothing more than contamination from mouse genes.

Ongoing research will hopefully clarify the (probably complex) relationship between XMRV and other murine retrovirsus with their potential to cause disease in humans.  In the meantime, the Journal of Infectious Diseases has written up a summary of the research so far and what the implications may be.  Although this summary is conservative, it is a fairly helpful guide.  This summary gives more background of the research involving prostate cancer, which may be more relevant to ME/CFS then it seems at first glance since ME/CFS leads to an elevated risk of cancer (often lymphomas or brain tumors), so the possible cancer connection is interesting to me.  The research so far on XMRV's role in prostate cancer seems to indicate that the mechanism by which XMRV acts to promote cancer is complex rather than the simple triggering of an oncogene, or insertion of a DNA strand to trigger the cancer, that some retroviruses are known to do. 

This report sheds some light on why the findings of XMRV ( and other MLVs) in the human population may vary so much.  "Several factors may contribute to the varied detection of XMRV in different populations, including geographic distribution, patient selection, analyte choice (DNA, RNA, antigen), and detection methodology."  Additionally, they add "viremia may be chronically low (as it is in HTLV), transient, or episodic, complicating detection."  The Journal then proceeds to list out measures that would help in the future to resolve the issues caused by the variability of detection so far including standardized assays, independently confirming results by sharing and retesting the same samples, doing prospective studies to asses which populations should be studied, and figuring out how the various Murine endogenous retroviruses are related to each other.  They also point out that when it comes to the challenge of finding and confirming specific disease causation, this is much more challenging to do with retroviruses than it is with other pathogens that have a more basic mechanism for causing disease.

This blog post entitled "The XMRV Hunt and Me" explores some of the possible reasons why a very sick patient may test negative but still have disease caused by this retrovirus.  Mary Schweitzer (a particularly knowledgeable patient and advocate) has pointed out on her blog that HIV was first detected in lymph tissue rather than blood, and as chronically swollen lymph nodes is a classic sign of ME/CFS, it might make sense to look there.  She also points out that evidence from France indicates that the virus may pool in the lungs.  The NICEGUIDELINES blog points out that because XMRV is slow-replicating it is important to locate reservoirs and the virus may need to be brought out of latency.

Here are some other interesting tidbits from the report:

"Analyses of XMRV sequences from different sources have revealed limited genetic diversity among patients. Because retrovirus diversity is dependent on cycles of error prone viral replication, the absence of XMRV genetic variability suggests that multiple cycles of infection are not taking place in humans."

"these data suggest that XMRV had zoonotic origins in mice but has replicated to only to a limited degree in humans."

 "With respect to therapeutics, XMRV is sensitive to some antiretrovirals in vitro [11, 20, 29], and there are calls for use of antiretroviral agents for therapy, even though early observations suggest XMRV replication may be minimal in humans."  This statement is followed by an admonition NOT to use these drugs on patients outside of carefully controlled clinical trials.  This idea has been hotly argued within the ME/CFS patient population for many reasons.