XMRV Buzz Nov 21st – Mice, Dr. Enlander and being ‘Undefeated’

November 21, 2010

Posted by Cort Johnson

The XMRV Buzz -short takes on the world of XMRV – will now be appearing regularly on the “Bringing the Heat” Blog

Unbroken – the Louis Zamperini and Laura Hillenbrand Story - no it’s not about XMRV but it is about Lauren Hillenbrand and that means CFS. She is a great spokeswoman for CFS and Louis Zamperini was a great vehicle for her next book, seven years in the making and which she says both brought her life and cost her physically.

A Mouse Model for XMRV - And now to one of the more interesting twists – developing a mouse model for an er…mouse derived virus? Of course we now know that XMRV does not appear to be found in the mice much (if at all) either in the wild or in the lab (which does kind of make one wonder how it managed to contaminate the WPI’s samples……if the worry was contamination from lab mice and it’s not actually in lab mice….then how did it???? Never mind)… the key with this study is that researchers have found a mice they can manage to infect XMRV with (it wasn’t easy), and now that they can do that they can make them ill, probe them, dissect them, feed them drugs, whatever….essentially the way is clear for the magnificent animal research establishment to go to town.

Thus far they’ve found XMRV in the spleen (expected immune organ), the blood (naturally) and the brain (most interesting)..(If mice have prostate glands and it was found in them they didn’t (perhaps out of respect for their privacy) report it was found there). The mice did recognize XMRV as something not good and did amount an immune response to it. Like humans their immune cells were able to knock it down with their all purpose XMRV transfiguring APOBEC enzyme…and that was that…..Now about those brain cells……where and what kind???

Dr Enlander Talks – Dr. Enlanders comments on the muddled state of XMRV thus far.

First he provides an insiders view on what we can now see was a very hastily done first followup study that appears to have broken speed records for study approval, completion and publication (thus implicating an nice swath of the UK CFS medical establishment in a rush to judgment… wouldn’t they have been smarter just to wait a month or two? Somehow they didn’t mind that everyone else would be agog at their ability to manipulate the process -which, come to think of it, may be the most telling thing – that they just didn’t mind ….Where would we be without the British? :) )

.He notes the both the differences and the close association between XMRV and the MLV’s found in the Alter study – a tricky and still unresolved subject and notes some shortcomings on the pro-XMRV side; despite it’s strong points the first study had some of its own, ahhh, issues (and how unbelievable is it that here we are, a year later, talking about the first study….) and the WPI’s lack of receptivity for whatever reason (and we have no idea, so let’s not even speculate) regarding his own proposed double-blinded XMRV study. He ends by noting something most ME specialists (and all patients) would probably agree with “All of us would love to initiate treatment’ – and let’s leave it at that. He is reportedly currently at work on a double-blinded XMRV study using multiple labs.

“I was asked to comment on the XMRV research. In Oct 2009 a virtually unknown Institute in Reno, Nevada, the Whitmore Peterson Institute, published in Science exciting research in which they claimed to have discovered a new relationship between the XMRV virus and CFS/ME. This was exciting news, we hoped it was the initial foundation of proof, that CFS/ME was a physical disease.

Within 6-8 weeks, miraculously, papers were in publication denying the original research. Usually it takes my Medical Center several weeks to allow a research proposal to proceed, followed by several weeks or months for the research to be completed and then several weeks or months for journal acceptance and publication. So I was astounded, as were others, at the time frame of the response, the journals and the relationships of the publishing research centers. Then a virtual boxing match occurred. This was to the detriment of all. One institute claimed poor cohort selection, another bad specimen handling, another claim related to lab contamination , stale samples that were stored for years, one even blamed the Chinese company that made the specimen tubes and so the complaints and cross complaints mounted. Harvey Alter, a research physician at NIH of ultimate repute, showed that indeed there was a MLV virus in CFS/ME specimens. This was countered by statement that MLV did not replicate the XMRV virus research. In essence this is true but the MLV virus and the XMRV virus has similar virion particles and/or cross reaction. Instead of certain research workers blasting this difference, it would have been opportune to investigate the relevance of the presence of either of these virions.

Both the protagonists and antagonists are not flawless. The initial research was not replicated in a double blind, multiple lab replicate study by independent selection. I offered, Whitmore Peterson, an independent replicate study of carefully selected Fukuda/Canadian criteria patients and controls between five viral labs. They were not interested. The whole matter of this research is puzzling, agenda seems to overpower the research.

All of us would love to initiate treatment, if indeed the virus was causal and if the treatment neutralized the virus. Lab research into non toxic neutralization in cell culture is incomplete and must be performed prior to using toxic anti-retrovirus treatment in patients. Action against XMRV should be explored in vitro of existing non toxic anti-CFS/ME methods viz; Ampligen, Kutapressin, Nexavir, Hepapressin, isoprinosin etc. In future I hope to see a united effort in exploring this devastating disease rather than a continuous boxing match – news that even our Utah XMRV/MLV expert was finding XMRV more complicated than expected”

6 comments

{ 6 comments… read them below or add one }

Abby November 21, 2010 at 11:13 pm

What Dr. Enlander fails to mention is the study would have been with 2 groups that did not have the ability to find XMRV in the first place . Moving forward not backwards is the goal of all in this field.

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Kop November 22, 2010 at 4:46 am

“Like humans their immune cells were able to knock it down with their all purpose XMRV transfiguring APOBEC enzyme..” This is incorrect. We don’t know enough yet. All we have seen is that some members of the APOBEC family can reduce XMRV infectivity. There are also studies that show MLV’s can evade APOBECC3, ‘Murine Retrovirus Escapes from Murine APOBEC3 via Two Distinct Novel Mechanisms’, or this study ‘The Glycosylated Gag Protein of a Murine Leukemia Virus Inhibits the Antiretroviral Function of APOBEC3′.

Of the studies looking at XMRV one study, ‘Apobec 3G efficiently reduces infectivity of the human exogenous gammaretrovirus XMRV’, found that “XMRV is resistant to human Apobec 3B, 3C and 3F…”

Another, ‘Inhibition of Xenotropic Murine Leukemia Virus-Related Virus by APOBEC3 Proteins and Antiviral Drugs’, found “the establishment of XMRV infection in patients may be dependent on infection of A3G/A3F-deficient cells, and cells expressing low levels of A3G/A3F, such as prostate cancer cells, may be ideal producers of infectious XMRV.”

And a third, ‘Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors’, found “A3G was able to inhibit the infection of XMRV to the same extent as Mo-MLV, more than 200-fold compared with the no-APOBEC control under these conditions. hA3B was also able to inhibit both viruses, but to a lesser extent, only 65- to 80-fold. All other human APOBEC proteins tested, hA3A, hA3C, hA3F (Fig. 2A), and hA3H (Fig. S2) reduced the infectivity of both viruses by less than 10-fold, despite being overexpressed at similar levels to those proteins that restricted infection (Fig. 2B). This result suggests that XMRV is susceptible to restriction by hA3G and hA3B. Although hA3B is poorly expressed in PBMCs (36, 37), hA3G is constitutively expressed…”

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Cort November 22, 2010 at 10:27 am

Thanks Kop for illuminating that. It looks APOBEC 3G may be the key to reducing infectivity of XMRV – thanks for that. That helped alot.

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Cort November 22, 2010 at 10:30 am

Yes, Aby but that’s how Science at its best works – you bring in all the major players and then let them duke it out, so to speak. I don’t know who Enlander was or did bring in but if he only brought in labs that had been able to find it – that would have been suspect to some people. Also it wouldn’t have told him anything about who was right and who was wrong. Notice that the BWG and Lipkin are using both the WPI and the CDC and the FDA/NIH labs

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LJS November 23, 2010 at 8:29 pm

FYI: The link on the buzz page to this blog is wrong, you have it as http://www.blog.aboutmecfs.org/ when as you know it should be http://blog.aboutmecfs.org/

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Cort November 24, 2010 at 2:11 pm

I swear I didn’t know! (why the putting the www on there makes it not work I don’t know) I fixed it :)

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