XMRV Buzz – the Infectious Pathogens Meeting…A Signature of Human Infection Found?

April 3, 2011

Posted by Cort Johnson

I missed the meeting and the video is not up yet but got Dr. Mikovit’s slides and Alex provided a summary as well. (This is a little late but we’ve had trouble posting to the website lately). The high point of Dr. Mikovits talk was her report of finding an human signature of infection in her XMRV samples.

Dr. Mikovits slides clearly state that XMRV is not an endogenous retrovirus but a new human virus but there appears to be a little twist (?) as one of her opening slides now states that “How XMRV got into humans is unclear” (or did I just not pick that up before?). The slides quickly move from the opening paper to the Lo study, noting besides its results, that they have been unable to produce evidence of an infectious virus. (That, of course, is what we believe they are trying to do now – either by growing the virus or showing that it is integrated into human DNA.)

Genetic Variability – Then comes genetic variability – a very important topic at the moment, The Lombardi paper stated that the gag sequences were basically identical to each other and to all published samples but here Dr. Mikovits states that further analysis shows more variability and in the next slide she shows how – the same patient can have more than 1 ‘XMRV’ infection; one of which was not picked up by the first PCR assay. Alex notes that 30% of ME/CFS patients have more than one strain.

Finding A Signature of Infection – Then she presents a simple but seemingly compelling answer to the contamination question. Researchers know that the APOBEC enzymes in human B and T-cells switch out amino acids in XMRV rendering it unable to replicate (in T-cells). Right now a good chunk of researchers appear to believe that XMRV is a laboratory creation that got into human samples but not humans. Geneticists are arguing that low variability in XMRV indicates it is not in humans…but what about a more direct measure? What about showing that the XMRV in your sample bears evidence of being altered by human enzymes…..ie the APOBEC enzymes?

Finding sequences that are consonant with APOBEC editing is like picking up a signature indicating that XMRV has been in a human body. In the next slide she shows evidence of just that; ‘hypermutation’ of XMRV sequences found in B-cells taken from human samples….! Dr. Mikovits focused on APOBEC editing almost a year ago noting that Grooms finding that such was going on enabled them to adjust their testing to better pick up XMRV. There are so many factors in XMRV that it’s hard to know how any one will play out but on the face of it makes sense that any XMRV that shows evidence of APOBEC editing should have infected humans at one time. It appears to be a strong argument that XMRV she has found has infected humans.

Then she shows that B-cell lines in humans can carry versions of XMRV that have been altered but can still replicate. That’s a big deal because other than the prostate nobodies been able to show a place where XMRV replicates. It’s also intriguing given the fact that EBV replicates in these cells as well and with the interesting study on Rituxumab (B-cell inhibitor) going on in Norway.

She then states that the challenge is to develop assays that can pick up all strains of XMRV. Of course the big problem is for the WPI has been other researchers almost complete inability to pick up the first strain – the one the WPI readily found in their original study – and which presumably did not exhibit APOBEC editing. If the research world could find THAT strain they would surely look for other strains.

Satterfield argues that recent assays should be picking up more strains of XMRV and MLV’s than ever. In an interview he notes researchers have antibodies to every protein and because of that they should be finding more strains of XMRV and a higher prevalence of XMRV than the Lomdardi study did. The most basic problem remains the inability of independent labs to find XMRV at all.

On the other hand – Dr. Mikovits finding of a signature of human infection in her samples seems quite compelling….:)

Antibodies - The next couple of slides show that antibodies to a variety of MLV protein detect XMRV – something some studies disagree with. Later studies, of course, are using antibodies to XMRV – not to MLV’s; two recent studies have not found antibodies to XMRV itself in people with CFS. On the next series of slides Dr. Mikovits points to new XMRV specific antibody tests under development and the detection of XMRV in a number of patients with cancer (leukemia, lymphoma) and blood borne diseases. She also reported that their new culture tests are much quicker (4-18 days vs 21-42 days)than their old ones and discussed the DERSE test and the INTERCEPT virus removal system for the blood.

Alex’s Overview – In his overview Alex notes that Dr. Mikovits has found high levels of viral proteins in patients.

Alex added a number of interesting points:

  • All 60 cell lines at the WPI have been tested for XMRV and are not contaminated.
  • Patient contacts including caretakers have higher risk of XMRV so this might be considered as a screening criteria for blood donations.
  • A question about XMRV transmission noted that an implication of CROI is that XMRV might be airborne. This is being investigated, but is not proven.
  • Mikovits is talking to Dr. Lerner about XMRV and herpes virus interactions. (No surprise there given the finding that XMRV is in B-cells.)
  • Mikovits describes ME/CFS as an Acquired Immune Deficiency.
  • A new high security lab may enable research they have not been able to do so far.
  • It was confirmed that Chronix have indeed claimed to have found fully integrated XMRV in ME/CFS, including flanking DNA on both sides of the virus.
  • Pathogenicity is not proven. However, it is suspected that antivirual methylation might be removed by epigenetic factors including those induced by the virus itself.
3 comments

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hopefulforcure April 3, 2011 at 5:02 pm

Wow,

Thanks Cort. This is very interesting.

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LJS April 4, 2011 at 7:26 am

Speaking of APOBEC3 Proteins, looks like there will be a presentation at the NIH about this…
http://sigs.nih.gov/VIG/Lists/Calendar/DispForm.aspx?ID=39

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John April 7, 2011 at 8:22 am

Just got through watching the XMRV part of the NIH meeting, from what I could tell it kind of looked like the ‘genetic variation’ being referred to is actually the Alter/Lo virus PMLV’s, ie a completely different virus (or viral-type sequences to be more precise) and not actual genetic variation in XMRV. What a crock.

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