Phase II of BWG Study is Complete (Really!) – The CFIDS Association today announced that the oh so important (and time consuming) second section of the BWG’s study focusing on sample preparation and sample storage is complete and that the results will be announced at the BWG’s meeting, just 3 days from now (Dec 14th) (gulp). The meeting is open to the public (if you happen to be in Gaithersburg, MD) but is not webcast; just three days later, though, a CFIDS Association webinar (register here) will feature two members of the BWG who will talk about the results and where they go from here.
Dr LeGrice reported they were looking at contamination issues although that has never been explicitly stated. Still, if contamination was to occur it would presumably occur during the sample preparation phase. At the very least the Group should be able to tell us how to prepare and store an XMRV sample such that it does not disappear. This suggests they should be able to indirectly tell us if any studies inadvertently destroyed XMRV during the sample preparation/storage phase. Discuss the meeting here.
Meeting Agenda – XMRV and the MLV’s will be the second topic on the meeting agenda. That discussion will take place from 1-3:30 pm EST. There will be nine presentations; Dr. Mikovits will make one of them. Here they are:
A. Introduction and Background, Indira Hewlett, Ph.D., DETTD, OBRR, FDA (10’)
B. Summary of Current Research on MLV-related Human Retroviruses and Disease Association, Jonathan Stoye, Ph.D., NIMR, UK ( 25’)
C. Recent Studies of Epidemiology of MLV-related Human Retroviruses:
i. U.S. Study, Shyh-Ching Lo, M.D., OCTGT, FDA (15’)
ii. U.S. Study. Maureen Hanson, Ph.D., Cornell University (15’)
iii. UK Study, Judy Mikovits, Ph.D. Whitmore Peterson Institute (15’)
D. Animal Studies: Potential Transfusion Transmission of MLV-related Human Retroviruses, Francois Villinger, Emory University (20’)
E. Update of Blood XMRV Working Group Activities, Graham Simmons, Ph.D., BSRI (15’)
F. Prospective and Retrospective U.S. Donor Surveillance Studies, Michael Busch, M.D., Ph.D., Blood Systems Research Institute (15’)
G. Assay Development Efforts on MLV-related Human Retroviruses, Rachel Bagni, Ph.D., National Cancer Institute (20’)
XMRV in Spain: Part II – details on the Spanish study have shown up and our surmises were correct; XMRV has been found in CFS, HIV and healthy controls in Spain. The sample size was very small – so any prevalence figures are very preliminary. This is not a ‘study’ so to speak; it was an attempt – after all the controversy – to see if they can find the virus. They were able to do that and it appears they will now start testing more people. We should keep in mind that they were looking for XMRV in an somewhat different set of cells- the B Lymphocytes – than everyone else has been looking in (PBMC’s). PBMC’s contain B Lymphocytes but no one has actually signaled out this group of cells and tested it.
It’s difficult to ascertain prevalence even in this small study because they reported the incidence of XMRV in cell lines rather than patients and some patients (n=11) obviously contributed more than one cell line (n=21). XMRV showed up in 3 x’s as many patients as controls using the env protein, in equal numbers of controls, CFS and HIV using the gag and twice as many CFS patients (50%) as HIV and healthy controls using the pol protein. The researchers noted the difficulty in determining prevalence -and that that was not their aim – but thought prevalence in CFS might end up, based on these early results, similar to the WPI – approximately 67%.
What we have here is a mishmash that indicates how uncertain the science is. Ideally we would want everyone who tested positive for one XMRV protein to test positive for another one. In fact, ultimately, that is how the testing will work – one positive test never denotes a positive; it has to be confirmed by another test. That is clearly not happening yet and a major goal, of course, will be to tighten up the tests so that consistent results are found across all of them.
They do suggest that B-lymphocytes could be a reservoir for XMRV; ie a place where XMRV is replicating more (or rather is actually replicating) and, in which, it is easier to find- which would be a really significant finding; however, the initial report stated the XMRV was found in very low amounts.
The most important to take away from this effort, though, is that the Spanish researchers have been able to find XMRV and they have found it in B Lymphocytes – an intriguing cell with the success of a small Rituximab trial and the herpesvirus infections found in some people with ME/CFS.
XMRV in Lymphoid Tissue in Macaques – They also showed XMRV can grow in the lymphoid tissue of Macaques . Lymph tissue is an area Dr. Mikovits has speculated could emerge as a reservoir ie a site of increased XMRV replication. That isn’t clear yet but the Spanish team did report that was no evidence that XMRV’s presence there was resulting in the deaths of immune cells -or altering immune functioning. Viruses often replicate furiously inside a cell, kill it and then swarm to the next one…Or the immune system recognizes an infected cell and responds to it. Neither of these scenario’s showed up in this early look at lymph tissues of macaques.
Functionality – The researchers did note, though, that XMRV could be interfering with cell functionality which actually fits in very well with ME/CFS. Immune cell numbers and composition do not appear to be radically affected in CFS – The Klimas/Fletcher studies, on the other hand, suggest that, cell functionality is quite impaired in NK cells and possibly T-cells which could be explained, on e would think, by a kind of smoldering infection characterized by low rates of replication. (Nothing seems to come easy in CFS….plummeting cell numbers aka AIDS would have quickly convinced researchers of the immune dysfunction in the disorder – and quite a few studies have been done – and they have never really shown up…Instead, impaired cell functionality has shown up – a much more difficult and subtle factor to spot.)
Huber and McClure Studies On Their Way – It almost seems like every upturn for XMRV is immediately followed by a downturn. Both Dr. Huber’s and Dr. McClure study – both of which are focusing on contamination – will reportedly be published in the near future.
A Still Missing Piece – the Alter/Lo Work – The sequencing work Dr’s Alter/Lo are doing will be very important given how critical their study was for XMRV. Further sequencing will nail down, presumably for good, where the genetic sequences they found came from. Dr. LeGrice reported that the sequencing would be ‘easy’ but he didn’t state how long it will take. Completely sequencing the virus was an important part of the WPI’s study. Shortly, hopefully we will get a definitive report on where the sequences they found came from; mouse or man?