You are probably talking about XMRV/MLVs.Good breakdown of the results, Cort. My reading is really slow these days. Thank you!
For how long have we people with CFS/ME been pointing out the Georgia cohort selected by several CDC researchers was invalid? The absence of evidence of any retrovirus in their "patient" population has no bearing on the other findings by researchers using samples from people who actually have the disease. There is no need to discuss the CDC findings any more. They are irrelevant.
The gag sequence they identified, however, is not specific to XMRV - it is a marker for a range of murine leukemia retroviruses of which XMRV is one.
The sequences in all four variants were more closely related to the sequences of polytropic mouse endogenous retroviruses (mERVs) than to those of XMRVs
"The sequence alignment and the phylogenetic analysis of the MLV-related virus env gene sequences obtained from both the
CFS patient and healthy blood donor revealed that they were also more closely related to those of polytropic or modified polytropic
MLVs than to those of XMRVs" Lo et al.
Although three MLV’s were found one MLV dominated the rest, infecting 86% of the CFS patients. One of the MLV’s was found also in one healthy control.
What is going with XMRV itself is not as important as it was before the Alter paper
While the WPI’s overall thesis was confirmed we still have two disparate findings; the WPI found XMRV and no other MLV’s while the Lo/Alter group found no XMRV and several other MLV’s. Researchers abhor impasses like this and they must eventually be cleared up. That the virus is exceedingly tricky is clear.
It’s possible but hardly likely that both findings are correct. It’s more likely, I would guess, based on the ‘swarm’ thesis, that the problem lies with the WPI findings rather than Dr. Alter’s.
Yes they did, here:The FDA response did not, interestingly, suggest that they believed other problems with methodology played a role.
"Indeed, it is possible that the PCR primers used in various studies may have different sensitivity in detecting the diverse group of MLV-related virus gag gene sequences that we found in the clinical samples. The 5′ gag leader sequence of previously described XMRVs represents the most divergent segment of the XMRV genome in comparison with the genomes of the other MLVs (4). In particular, there is evidently a unique 15-nt deletion in the 5′ gag leader region in all of the XMRVs previously identified in patients with prostate cancer and CFS (3, 4). To detect XMRVs in human samples with better sensitivity and specificity, some studies used a PCR primer spanning this unique deletion as the “XMRV-specific” primer (6). However, none of the viral gag gene sequences amplified from the blood samples of CFS patients and blood donors in our study has this particular deletion (Fig. S1). As a consequence, such primers might have been insensitive in detecting the MLV-related gag gene sequences that we have identified." Lo et al.
No, that's not correct.
Remember it takes a while for things to be published.
The patients were seen in 2003.
The paper on them is what started the "empiric" definition:
http://www.biomedcentral.com/1741-7015/3/19
I think you're getting confused. The CDC say that the empiric criteria are just an operationalised version of the Fukuda criteria. That's why they say the prevalence is now 2.54%. That's what they say in all the papers using the empiric criteria - they don't say they're using a different set of criteria.
That is partly my point. Although the people who were diagnosed as CFS (empiric) in http://www.biomedcentral.com/1741-7015/3/19 may never have satisfied the ordinary Fukuda definition in 1997-2000 as they also brought in ISF, CFS MDDm (i.e. hadn't been given the diagnosis of CFS because they previously had melancholic major depressive disorder). The paper at http://www.biomedcentral.com/1741-7015/3/19 doesn't make things as clear as it should.
Unless we know that the blood was taken from them between 1997 and 2000, rather than 2003 (when they did all the testing), we should assume that they all are just "empiric" criteria patients.
The Alter/Lo group did not do that, citing the difficulty of having to wade through from hundreds to 1,000’s of cells in order to find the one infected with MLV’s. (Yes, it is very rare in the blood!).
Found on XMRV Global Action Facebook 5 posts down
http://www.facebook.com/pages/XMRV-Global-Action/216740433250
Remember that it was not just those that those that were brought in. ISF, CFS but MDDm, ISF but MDDm, controls were brought in. One can see it in: http://www.biomedcentral.com/1741-7015/3/19/They had to use a group of patients to figure out the parameters of the Empirical definition; the patients they used were first identified as CFS patients under the Fukuda definition. Remember that those patients were identfied in 1997-2000 long before the Empirical definition was even a theory. Those were 'Fukuda' patients.
You can't assume that they used a definition that was published in 2005 on patients whose samples were taking in 2003. That is assuming too much.
http://www.biomedcentral.com/1741-7015/3/19/The study was conducted from December 2002 to July 2003
etc.Data came from a 2-day in-patient study of 227 people with CFS, with other chronically fatiguing illnesses, and matched non-fatigued controls identified in the general population of Wichita, Kansas.
Details of our two study populations have been
described previously [2,26,27]. Briefly, between 2002 and
2003 we sampled adults 18 to 59 years old from Wichita,
Kansas [26,27] and between 2008 and 2009 we sampled
adults 18 to 59 years old from metropolitan, urban, and
rural Georgia [2].
My initial post was relatively gentle.Please back off people. Yes, there were errors; there is confusion. Cort was reporting, with considerably higher fidelity than mainstream media.
I'm sorry but Cort is confused, he is not sticking to the facts. This needs pointing out as quikly as possible, otherwise misinformation spreads and we are again at the mercy of the the Wessely's and Reeves.
While a number of people, (myself included,) have mentioned viral infection of mitochondria, I want to make it clear this is not as straight-forward a question as it may seem. Most of the time you don't find a virus infecting mitochondria. Murine Leukemia Virus itself is the one exception I've heard about, in mice.
The general rule has become almost dogma in some minds. This is because most of the time it is true. As anyone with ME/CFS should know, when exceptions occur they can be very important. The medical school rule of thumb "When you hear hoofbeats, think horses, not zebras." is handy for overly imaginative students, but researchers need to notice things like donkeys, mules, zebras and even the occasional okapi.
Here's my inexpert opinion on why you don't commonly find viral infections of mitochondria:
1) Many virions are physically too large. (You likely can't park a tractor/trailer in your garage.)
2) Even if the virion will fit, the entire viral genome may be too large and complicated to fit in a plasmid mitochondria can cope with. The limit seems to be something less than 10,000 base pairs, perhaps near 8,000. There are relatively few viruses with genomes that small.
3) Even if the virion and viral genome will fit, the process of converting the information into molecules which form the virion may require more sophisticated support than is available inside a mitochondrion.
This last point sounds obscure, but it can be illustrated with a gotcha in common modern computer technology. Consider the cellular machinery which translates DNA as an operating system. For the whole cell, we have something like Windows 7 (tr), with support for all kinds of obscure things needed for compatibility with older versions. For the stripped-down machinery of mitochondrial transcription, we have something like the OS of a Palm Treo (tr). If you have tried to run a Windows (tr) application on a Palm Treo (tr), you might guess a few support libraries are missing. (I could go further and compare the complexity of a complete cell to what system programmers call "DLL Hell". This, however, takes us away from the central point here.)
The bottom line is, yes, it could be true; no, it doesn't happen often or easily.
Real researchers will have to take over from here.
Disagree. I would like to point out that Cort has made some objective observations that make sense. Maybe you don't agree with all of them, or they are not what you want them to be, but his analysis makes sense based on the limited knowledge we actually have.
His frequent mention of contamination is another tactic of the denialists. .
Jeeeesh people seriously...
This stuff is super difficult, especially for the brainfogged ( like me). I apreciate all the hard work that Cort does and I love reading his articles. I am sure they are not perfect and contain some assumptions or errors that is unavoidable at this stage. Great if people can point these (assumptions/mistakes) out and improve the info out there. But the personal attacks against Cort, I find them very distressing. He is not the enemy, he is human, allowed to make mistakes and allowed to have unpopular opinions if he chooses to. I can't explain it well but this all makes me so sad.
They also found 4 MLV's, not 3, and even that is misleading
That's is not accurate. I cannot find the source right now, but that makes them sound lazy. They only believed that there was no reason to delay the paper.
This study was a big breakthrough. It demonstrates that there are most likely problems with the other studies. I'm stunned that you keep saying that they were all looking at the same genetic sequence, as if that ruled out problems with geographical distribution and mutation. Never mind the fact that none of the negative studies calibrated their tests to a known human sample.
I would also like to see a reference to this?