The individual with CFS type 3 sequence contains an insertion of a C residue within the ORF [Fig. S1(1)]. This leads to a reading frame shift within aa 166, the premature termination 15 aa later, and, consequently, a truncated Gag protein. It is difficult to imagine how such a virus could persist in the host without a closely related helper virus.
The technical abbreviations here are aa = amino acid, ORF = open reading frame.
This pitch is not so much aimed at Lo/Alter as at the infectious agent itself. How dare it persist in this defective form? We now have a variety of helper viruses with the full Gag sequence available. We see considerable sequence variation in available data, suggesting variation is common, if not inherent. The explanation is already shaping up nicely.
FoI request to Imperial College London ref XMRV serology test
Following Professor Myra McClure's statement (in the Q&A session of the 1st International XMRV Workshop ) that "We've now done the serology", a Freedom of Information request was submitted to Imperial College London on 10th September 2010 to identify whether they had developed a serology test for XMRV. This included the following.
(i) Confirmation of whether Imperial College London has developed a serology (anti-body) test for XMRV (xenotropic murine leukaemia-related virus).
(ii) If this test is for both ME (also known as CFS) and prostate cancer combined, or for just one of these diseases in isolation, or if there are separate tests for each of these diseases.
(iii) If this test detects anti-bodies to all MLVs (murine leukaemia related viruses) or just XMRV.
(iv) If this test is used for research purposes only or if it is available commercially or if there are plans to make it available commercially.
(v) If this test has been developed for specific research purposes within Imperial College London, or other research institution, and if these research purposes will be published (e.g. in a science journal or on the college website) and when.
(vi) How long the test has been in use (for research purposes or otherwise).
The following response was received on 27th September 2010.
"Further to your Freedom of Information request, Imperial College has not developed a serology (anti-body) test for XMRV and therefore the remaining questions (ii - vi) are not applicable."
It is unclear, therefore, which/whose XMRV serology assay is being used by Professor McClure and, given that it has not been developed by the Imperial team itself, how they are able to vouch for its reliability. If the assay in question has been proven empirically to detect XMRV antibodies and, given the growing number of UK patients who are testing positive via the Whittemore Peterson Institute/National Cancer Institute's methods, Imperial's continued failure to detect the retrovirus implies that either they have a flawed sample cohort and/or (as discussed at the 1st International XMRV Workshop) they could be using contaminated test tubes.
QUOTE (from Cort): "Well after the Workshop she said she would trying culturing (using a phelbotomist (?) gather blood from WPI patients) and who knows if that went through. I sure would feel funny giving samples to her, though." END QUOTE.
McClure has possible access to CFS patients from a clinic that is run by Imperial Colleage. She said that she wouldn't do any further CFS research (in the Australian interview) but obviously loves the limelight.
If McClure did want to do further research on these patients (and it passes the ethics committee etc), then there are enough patients who attend that clinic and are not up on recent developments for her to take her pick.
Nice one Tina! This does sum up the general chaos, frustrations, misunderstandings and talking at cross purposes. (Kept wishing he'd actually hit the guy with a rubber bat though! - guess I've been watching too many cartoons! V appropriate given the title of Cort's article too!)
I'm getting kind of fed up with this "contamination" business. Let me put some questions on the spotlight:
- if so, does this mean that the studies that came out negative were done in laboratories that have better cleaning teams than the ones with XMRV / MLV positive results?
- does this mean that the negative results came out in laboratories that don't experiment with mice?
- does this mean that, where positive results were obtained, they (sort of )"rubbed" most of the CFS samples on the contaminated tables, but only a few of the control samples?
- if it happens that the samples were contaminated with mice virus because they use mice for testing other things, how come they didn't find also rabbit viruses o ape viruses, which are ALSO used on a regular basis on laboratories?
C'mon scientists! Be serious about this!!! If you have arguments against the positives studies, set them out so they can be discussed, but don't use arguments that even I can put upside-down! We patients are not nave nor ignorant, don't insult our intelligence, please!
Contamination by tiny traces of DNA can occur in exceptionally subtle ways, but experienced researchers plan on this. They test reagents and equipment before running experiments, even if they believe they have prevented contamination.
Clinical samples from actual patients are messy, if there is an immunological defect they will probably have multiple infections. This requires a great deal of patience in separating the signal from the noise. What we have here is a group of researchers who said, "this looks like contamination, we aren't going to waste time looking further." We also have researchers who said, "these look like endogenous sequences, we aren't going to waste time sorting them out."
It is predictable they would miss a retrovirus 94% homologous to MLV and 95% homologous to an ERV sequence. That they would not apply critical intelligence to their own assumptions is depressingly familiar. As I've said before, you can eliminate all positive results due to contamination by eliminating all positive results. This proposition can be verified without expensive research.
The question about about the defective virus, quoted above, does contain food for thought, if you reverse the assumptions. Once a retrovirus inserts genetic material, the provirus will remain as long as the infected cell survives. It doesn't matter if the sequence is defective, the cellular machinery will keep churning out copies whenever those genes are active. It is possible most of the viral material found in infected humans is defective, as a result either of inherent low fidelity in viral transcription, or because of hypermutation caused by host cell defenses.
If we assume this, for the moment, we would predict low viral load, (since most sequences are not competent to reproduce,) and a bizarre variety of effects, not restricted to those produced by competent virus. Different classes of infected cells would have different lifetimes, after which the infection would appear to remit. Since those known competent viruses have sequences for receptor elements associated with stress or sex hormones, the illness would likely reappear under specific conditions. At this point we don't know the expected lifetimes of different classes of infected cells, but there are enough cells in the immune system with lifetimes in the range of relapsing/remitting episodes to make this a useful hypothesis.
At least to this layman, this sounds very similar to clinical experience with the actual illness, which was lacking in the groups which found nothing.
Cricket? Cricket? Is that not a little bug that squeaks?? :tear:
(I feel I am dangerously close to the stereotype of the unknowledgeable American...)
No, pitiful attempts at humor aside, I know little of cricket - the other big bat and ball game.......Maybe that's why the Brits lost so badly this time..maybe they were 'out of their league' or as Cloud so cleverly puts 'playing a different game'.