This study did not confirm the existence of XMRV in the UK; first of all, they did not do an 'antibody test' as one is used to thinking of the term. They did neutralization assays, giving hypothetical antibodies in the patients' sera the chance to prevent XMRV from infecting cells, and compared the results to a previous run of the same assay with known XMRV-specific antibodies (not from these patients' blood) which they feel they had established really COULD
specifically block XMRV infection.
Some controls and one CFS patients' samples were able to reduce the overall level of XMRV infectivity according to this neutralization assay, so they tried to see if this was really due to an antibody genuinely against XMRV in these patients or to an antibody (or antibodies) that just happened to block XMRV but was produced by the patients to some
other virus that merely "resembled" XMRV in some places. After this further test, it seems that using their basic assay methodology, the prepared (known) antibodies were specific for XMRV, but those in the patient sera were
not; the latter blocked all the viruses the team threw at 'em.
They took this result and, combining it with their negative PCR results, concluded that the patient sera very likely did
not contain antibodies to XMRV, but to some other virus that merely shares some key sequences (and therefore key antigen/s) with XMRV. That interpretation means NO solid evidence of XMRV even among the controls.
Whether their interpretation is correct is open to some question, mainly because it hinges on the quality of their PCR test. (Did they allow enough time to culture the 'virus'? etc)
Also, as the authors themselves said, the fact that more controls were 'positive' for neutralization was odd, so they threw out a hypothesis I find a bit questionable:
Is the bolded statement necessarily true? It assumes that XMRV will always replicate at a higher level when immunity is compromised in that special CFS way. No one has demonstrated this to be the case, to my knowledge.
[I also wonder which other virus they believe those neutralizing sera were responding to, i.e. how common are viruses that share XMRV, MLV, etc sequences (not limited to those that code for the retroviral envelope protein, either)? I'm not a virologist, so I really don't know; in absence of that knowledge I just find it odd that XMRV would be neutralized so noticeably by antibodies to some other virus.. if it's an ERV, it's a bit strange that the antibodies would also neutralize the VSV-env MLV pseudotype.]
Anyway, even if XMRV is involved in just a subset of cases as they propose, then it is all the more necessary to select patients that match the WPI cohort as closely as possible, incl. using the Canadian criteria and sampling patients from a wider geographic distribution.
I agree with everyone, including the authors of this paper, that the key now is to find out why the different labs' techniques are yielding such different results. Is it the methodology or the samples? Collaboration, especially in testing known positives from the WPI vault, is the only answer. And in that regard the best nearest hope is the collaboration already underway under the auspices of the DHHS, with Dr. Mikovits on the Task Force (see Jennie Spotila's post earlier in this thread!) THAT is what I'm really waiting for.
(Btw, as others have mentioned, whatever happens it does seem most likely that the WPI found SOME virus, so even if it is established that XMRV is not what they found, the DHHS should not be able to avoid the question of what then
was found... and then we'll have another round of 'fun' ! So we should not get manic this early in the game folks -- the terrain will keep shifting, so each of us needs to seek a comfortable equilibrium.
)
