UK researchers are not winning the hearts and minds of CFS patients – that’s for sure. Just a couple of uplifting weeks after Dr. Mikovits displayed so much enthusiasm and confidence in XMRV the other shoe has dropped. An Imperial College researcher said another negative study was coming and here it is; this UK study also failed to find virtually ANY evidence of XMRV in a large number of CFS patients. This study was similar and different from the Imperial College study.
Annette Whittemore said to be cognizant of who’s doing the studies – in this case, though, there doesn’t appear to be any bias to question, no damning history of behavioral emphasis to reflect upon; two members of the study, Dr. Kerr and Dr. Gow, are long term ME/CFS researchers committed to a pathophysiological interpretation of this illness. (Ironically it was Dr. Gow that refuted Dr. DeFreitas finding 25 years ago).
Indeed, the paper went to some lengths to praise the Lombardi Science paper stating the “apparently compelling evidence against the possibility of laboratory contamination” and the immune response against XMRV the researchers demonstrated was present. They stated that they set out with ‘the intention of confirming the Lombardi’ study.
PCR Tests – This was a large study that looked at well over 500 CFS patients and controls from two cohorts in the UK and Scotland. They first looked for sequences on two the three genes XMRV possesses. When they didn’t find anything the first time they looked again using a more sensitive assay.
Immune Tests – Unable to find evidence of XMRV by PCR they looked for signs that the patients immune systems were reacting to it. To do this they obtained some ‘neutralizing antibodies’ against the ‘env’ protein found in the family of mouse retroviruses. Antibodies neutralize retroviruses by attaching to them and preventing them from getting their hooks into cells. They also raise a red flag to the immune system to come and attack. As they examined this set of antibodies they were able to identify one that was specific for XMRV and they used it to search for the virus.
The neutralization test is a rather indirect one; they apparently add the antibodies to the sample and then (somehow) test the sample for ‘infectivity’. Since the antibodies attach themselves to the retroviruses the degree of infectivity should go down a certain amount and in a couple to test cases they confirmed this. When they ran the neutralizing antibody test on the 142 ME/CFS patients none of them met the criteria for infection. Ironically, 14% of the healthy controls from one of the healthy cohorts tested positive for infection, altho later testing suggested it was do to a different mouse virus.
They stated that they were ‘confident’ that their ‘PCR assay is more sensitive than the published single round PCR method and should have possessed the necessary sensitivity to find XMRV’.
Two Different Tests : Two Different Results – The WPI has backed away from the PCR test because of its inability to detect XMRV at very low levels and their associated lab VIP Dx is not longer offering it. This could not be a reason, of course, for the zero results seen in this test – the WPI’s PCR test may not be perfect but it appears to be able to find most instances of infection. We also know from Dr. Lombardi and from patient reports that the WPI’s test IS finding XMRV infection in UK patients. Why they are finding it and two UK groups have not, is, of course, the big question. Either the patients are very different or the tests are. Since it seems unlikely that that the patients are THAT different its pretty clear that the WPI’s test is quite different from these other groups.
Validation Not a Replication Study – It’s interesting, by the way, that this UK group – with its ties to the WPI via Dr. Kerr – did not appear to avail itself of the WPI’s assays or or Dr. Singh’s antibody tests. Since the group didn’t appear to use the WPI’s methods this is a validation study not a replication study; its was an attempt to validate the WPI’s claim that they’d found XMRV not an attempt to determine if the the WPI’s methods worked.
This is still just the beginning of the XMRV studies to come out but its a remarkable turnaround given the lengths the WPI, researchers from the NCI and the Cleveland Clinic went to in that compelling Science paper (Dr. Coffin called it as good a first paper as they get) to demonstrate the presence of XMRV. The fact they were able to show that this virus was able to infect previously uninfected cells and show a virus budding out of them still seems – at least to this layman – to be the most singular and important finding to date.
My understanding is that the WPI is now using Dr. Singh’s antibody test specific to XMRV that shows INCREASED not decreased rates of positivity. It really is a conundrum; the WPI appears to be getting more and more internal evidence that they’re right these papers are coming out suggesting that something went wrong. The first question always appears to be if what the WPI found is an endogenous retrovirus – a piece of junk DNA from an old mouse retrovirus in our genome. They sequenced 2 and a half strains of the virus and compared what they found against our entire genome against our entire genome and found nothing. That’s one of the reasons Science took the paper – they convinced them it was not an endogenous retrovirus. But if it’s not that then what is it?
The Scientific Director of the CFIDS Association, Dr. Vernon, will reportedly release an analysis of the study tomorrow, giving us a much needed expert overview of the situation.
- The complete paper
- ME Association’s brief response
- Professor Racaniello’s Virology blog on the study
- Discuss the results