XMRV Buzz (Dec 21st): The Retrovirology Papers Day II

December 23, 2010

Posted by Cort Johnson

The Retrovirology Papers: Day Two – Not surprisingly the media jumped on the titillating but wrong story and stated XMRV was done and that it was not the cause of ME/CFS. XMRV certainly did take a hit, yesterday, but several important names, particularly Dr. Coffin – who was a co-author of two of the papers , and has been doing his own research on how to tell XMRV apart from a contaminant, refused to fold XMRV’s tent stating that the arguments against XMRV were subtle and indirect and that none of them directly indicated the WPI had inadvertently come with a contaminant.

Indeed three of the four papers demonstrated that they had found a contaminant but not that the WPI did. The Robinson paper indicated that one test for contamination that neither the WPI or the Lo lab used(?) was more sensitive than the mtDNA test that the WPI reportedly used. But it was only MORE sensitive; even if the WPI or Lo study mischaracterized some contaminated samples there was nothing in the report to suggest that they mischaracterized ALL of them – something that doesn’t appear to be even remotely tenable. Similarly, the Oakes paper described a situation where tests for contamination revealed that yes, contamination was present. It’s certainly a warning but both the WPI and the Alter studies tested for contamination and they did not find it.

The Hue paper - was the only potential body blow to XMRV of the four. Dr. Hue’s phylogenetic analysis suggested that XMRV was not derived from a wild mouse but came from a cell line grown in a laboratory. Hue’s argument was that if XMRV was a human pathogen that is widespread in the population – as studies suggest it is – then it would have, like HIV, and other viruses picked up a great deal of variability. But Hue found that XMRV was actually less variable than the 22RV1 cell line his analyses suggested it was derived from. Hue, however, only used two full length XMRV genomes for ME/CFS patients in his analysis. Whether or not he needed more is unclear – he also used 1 representative of other mouse viruses in his analysis but it does make one wonder about the many unsequenced strains sitting in the WPI’s labs. Whether including them might possibly have altered his results is a question for a population geneticist….

Hue also showed that the standard PCR test for XMRV was not as specific as had been originally thought and that it can misidentifies endogenous MLV sequences from some mouse strains as being XMRV. The misidentification is something of chimera for the WPI; the fact that they could grow viruses indicated that they did find XMRV. The WPI countered with the fact that a) they can grow the virus – so the PCR results were not simply the result of some mouse DNA getting into their samples and that their antibody test indicated an immune response had been created to a virus, not a contaminant. They did not reply to concerns about Hue’s phylogenetic analysis.

Dr. Racaniello Does a Partial Turnaround – To read that Dr. Racaniello said that XMRV’s course in CFS was probably over was rough, considering that he has been considered to be an objective source. Over night, however, Dr. Racaniello reconsidered his opinion and the next day concluded that, while his concerns remained, he had overstated “I do not believe that the four Retrovirology papers prove that XMRV is not involved in human disease.”

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