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XMRV is neither a cause of CFS nor a threat to the blood supply

Jemal

Senior Member
Messages
1,031
The scientific method at work: xenotropic murine leukemia virus?related virus is neither a cause of chronic fatigue syndrome nor a threat to the blood supply

Matthew S. Karafin, Susan L. StramerArticle first published online: 12 JAN 2012

DOI: 10.1111/j.1537-2995.2011.03518.x

http://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2011.03518.x/abstract

The first page of the article is available on their site. Can't easily quote from it though. The rest of the article is behind a paywall.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
XMRV is neither a cause of chronic fatigue syndrome nor a threat to the blood supply

12 January 2012: http://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2011.03518.x/abstract

'The scientific method at work: xenotropic murine leukemia virusrelated virus is neither a cause of chronic fatigue syndrome nor a threat to the blood supply'

Am gonna shove this here because it isn't research per se but a commentary from 'Transfusion' the American Association of Blood banks.

The extract is there to read and I am reading the full paper now. It doesn't say anything more than we know or would expect I guess, but I will perhaps shove some extracts here if I think they're worth a mention.

Thanks Jemal for flagging it by the way. I don't think you've posted it here yet.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
Here's a bit - in context but highlighted - that I wouldn't mind some help understanding please:

'Perhaps most importantly, Paprotka and colleagues4 proposed that XMRV originated as the result of a laboratory recombination event involving two mouse proviruses that occurred during the serial passage of a human prostate cancer xenograft (CWR22) in nude mice in the 1990s. When aligned, these two proviruses were identical to the sequence of XMRV. Thus, the authors concluded that XMRV is not a real human pathogen and that positive findings were the result of contamination by a laboratory-derived virus.4

In a subsequent related study, it was shown that both proviruses occurred in laboratory mice but not in wild strains of mice, and no laboratory mouse strain could harbor XMRV replication due to the lack of the required receptor in laboratory mice, indicating that the xenografted human tumor cells were required for XMRV propagation.13

So here the research had suggested that XMRV could not exist in laboratory mice without the presence of the human tumour cell because of the absence of a 'receptor'. Right? And of course that XMRV doesn't occur in wild mice anyway.

'In addition, the genetic distance among env and pol sequences from the persistently XMRV-infected prostate cell line, 22Rv1, derived from the CWR22 xenograft, exceeds that of patient associated sequences, suggesting laboratory contamination versus human infectious transmission. Thus, XMRV derived from the 22Rv1 cell line is the genetic ancestor of all subsequent isolates from CFS or other patients.14'

Right so, what they found in patients is the same as what they found in tumour-mice i.e. the same XMRV and not something that is any different. So it hasn't been 'processed' by the human body as one might expect if indeed it were present in humans as a pathogen. Is that right? Sorry for my use of language - lol - am clearly no scientist!

13 Cingoz O, Paprotka T, Delviks-Frankenberry KA, Wildt S, Hu WS, Pathak VK, Coffin JM. Characterisation, mapping and distribution of the two XMRV parental proviruses. J Virol 2012;86:328-38.

14 Hue S, Gray ER, Gall A, Katzourakis A, Tan CP, Houldcroft CJ, McLaren S, Pillay D, Futreal A, Garson JA, Pybus OG, Kellam P, Towers GJ. Disease-associated XMRV sequences are consistent with laboratory contamination. Retrovirology 2010;7:111.

I do actually prefer these kind of summary's though (as a non-scientist and patient). At least the language is generally easier to understand. Kind of like why I follow TWiV I guess and other blogs etc. who do the same. Of course it helps to have more than one interpretation of anything - helps to prevent bias or lessen it at least ;)
 

rlc

Senior Member
Messages
822
Hi Firestormm,

RE Right so, what they found in patients is the same as what they found in tumour-mice i.e. the same XMRV and not something that is any different. So it hasn't been 'processed' by the human body as one might expect if indeed it were present in humans as a pathogen. Is that right? Sorry for my use of language - lol - am clearly no scientist!

Yep thats right, the conclusions that they have come to is that XMRV is artificially created in the lab, and what was claimed to have been found in CFS patients is identical to this lab creation, and has not been changed in anyway by being processed by the human body, as happens to all other viruses that infect humans. Which has left them with the only possible conclusion, that XMRV was never in humans, it was in the laboratory equipment used for the study and PCR then amplified it, making it look as if it was in CFS patients. But it wasnt.

All the best
 

RRM

Messages
94
Perhaps this may complicate things even further, I am gonna tackle the bolded sentences in parts. ;)

In a subsequent related study, it was shown that both proviruses occurred in laboratory mice but not in wild strains of mice
XMRV is not found in wild mice, as you correctly note (but that was already reported in the original Paprotka et al. study). However, this quote refers to the fact that no strain of wild mice even harbors both preXMRV1 and preXMRV2. Basically, it makes the formation of XMRV in nature hard to imagine, as only (some) lab mice contain both strains that together form XMRV.

and no laboratory mouse strain could harbor XMRV replication due to the lack of the required receptor in laboratory mice

Like I said above, although any strain of wild mice lacks both preXMRV1 and preXMRV2, there are some lab mice that harbor both ancestors of XMRV. However, if the "XMRV recombination" between preXMRV1 and preXMRV2 did occur in one of those lab mice, the resulting XMRV would not be able to replicate in this lab mouse.

indicating that the xenografted human tumor cells were required for XMRV propagation

Taken together, it means that a) it happened in the lab but b) that it couldn't have happened in a lab mouse, and thus it must have happened during "mixing" these mice with a human cell line that, unlike lab mice, would facilitate XMRV replication (like 22Rv1).

As for the second part:
'In addition, the genetic distance among env and pol sequences from the persistently XMRV-infected prostate cell line, 22Rv1, derived from the CWR22 xenograft, exceeds that of patient associated sequences, suggesting laboratory contamination versus human infectious transmission.

This is a pretty straightforward experiment. When a virus replicates, some random mutations occur. Regardless of the amount of diversity (for instance, HIV mutates far more than HTLV-1), you would expect that any single virus would be less diverse in a human cell line than in a "real" human (which is a far more "hostile" environment). With XMRV this is not the case: letting the virus replicate in a "easy" environment like 22Rv1 still results in more sequence diversity than the diversity reported in human samples. This suggests contamination rather than infection.

Thus, XMRV derived from the 22Rv1 cell line is the genetic ancestor of all subsequent isolates from CFS or other patients.14'
Although the conclusion is right, it's founded by more arguments than what was previously mentioned. Especially the phylogenetic analysis, which is not mentioned in your quote, is strong evidence of 22Rv1 being the ancestor, and should really have been mentioned in this context, IMO. But perhaps the authors did - I have only read your quotes.
 

Jemal

Senior Member
Messages
1,031
Thank you all and apologies Jemal I did look - swear I did. Have asked for the threads to me merged.

No problem and no need for apologies. It's good to have several people posting about new XMRV articles.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
This was the next bit that followed my extract above. Pretty self-explanatory I suppose though I had seemingly lost my knowledge of the studies they refer to I am afraid:

'XMRV also does not appear to be a concern for blood recipient safety. Studies have recently demonstrated that XMRV would not be able to persist or replicate in human blood due to cell-mediated antiviral pathways.9

A large recent study further demonstrated that no XMRV antibody could be detected from 17,249 blood donors or recipients, including 13,399 US blood donors from six different regions and 3741 donors linked to 109 recipients of which 830 samples were tested over a 2-year period.

A positive antibody result required reactivity to three different XMRV proteins, and the tests used were the same as those used by the SRWG and represented those tests that were automated and could be used for blood donation screening if needed.


Since RNA could also not be found in any recipient or any donor with isolated antibody reactivity, the study concludes that XMRV is not a current threat to blood safety.15'

15. Dodd RY, Hackett J, Linnen JM, Dorsey K, Wu Y, Zou S, Qiu X, Swanson P, Schochetman G, Gao K, Carrick JM, Krysztof
DE, Stramer SL. Xenotropic murine leukemia virus-related virus (XMRV) does not pose a risk to blood recipient safety. Transfusion 2012;52:298-306.

That section underlined above from a layperson's (my own lol) perspective means that RNA (once of the key components of retroviruses) could not be detected then in the blood of those tested even those who showed some 'isolated' antibody response. Is that right? They tested all the blood against three proteins of XMRV and there was effectively no response of clinical significance found.

I tell you it is incredible - still - how much I forget having read or being made aware of. This study went right out of my mind even though a reply I had the other day referred to it - if somewhat obliquely. Damn. I should have stuck with financial markets! :D
 

currer

Senior Member
Messages
1,409
I'm glad they are telling us what to think. It saves all the strain of trying to think for yourself.
 

currer

Senior Member
Messages
1,409
As I remember the Lo and Alter paper, the genome of XMRV is a mix of european and asian (fancy) mice.

So it must come from lab. mice, it cannot have arisen in the wild, as lab mice are a mix of fancy and european strains.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Hi currer, this was addressed in a very early paper, I forget the name. The asian and european (9?) mice could indeed mix. It is highly probable that the asian mice made it to California during the gold rush days. So the mice populations could have interbred.

Also there is an untested assumption here. PreXMRV1 and PreXMRV2 migth or might not be the only two MLV strains that could recombine to make XMRV. There are probably thousands of strains out there. I am very sure that not every possible strain has been tested, expecially in regard to recombination events in the wild - especially since a recombination between more than two strains over multiple generations can happen.

Bye,
Alex
 

currer

Senior Member
Messages
1,409
The diversity reported in human samples - which is being used as an argument against natural viral replication in humans - could be an artifact either of selection pressures by APOBEC or replication by mitosis in PBMCs.

If XMRV is dependent upon the cell it is integrated into for its replication (eg. PBMCs) it will replicate itself with fidelity and thus not show the diversity these authors pretend to expect it to.

These arguments are specious in my opinion. There are good reasons to expect that viral diversity in a host will be responsive to selection pressures from the immune resoponse of the host and thus be quite different from the diversity in a cell line.

The authors of this paper know there are many possible answers to the problems they cite, and that their reasoning is not as definitive as they wish it to appear.

They are simply attempting to close down research and end public curiosity in this subject.
Reasoning away "xmrv" will not provide real answers. Only further research can do that.

I have some doubts about virology as a profession. Many virologists work in bioweapons research, those that do not, work manipulating organisms in potentially damaging ways, they all experiment on animals, they close ranks when threatened and treat the public with disdain, they can potentially earn vast sums from patented organisms - God knows what organisms they are making and what the end result will be. They are probably required to keep secrets about their work from the public - how honest are they likely to be with us?


Quite apart from the real question at issue, which is never posed - that "xmrv" is a lab artifact and the real infective retroviruses are quite divergent from this sequence - rendering all their careful reasoning away of "xmrv" fallacious.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Currer, it is indeed likely that the dominant mode of infection for such viruses is clonal expansion of B cells, although direct cell to cell transfer may occur. The virus will not undergo much if any change during clonal expansion events. If free virions are damaged by restriction factors, the the majority of subsequent virion release will be from the old established clonally expanded cells. This will stabilize the viral population to a standard strain, and vastly slow viral adaptation and evolution. This is entirely consistent with what we know of MLVs. MLVs are not HIV, the lessons learned from HIV have limitations with respect to MLVs.

If XMRV from infected labs does get to infect people, it could produce major problems years down the track. I wouldn't expect to see it produce major problems quickly - the incubation period would make HIV look like the proverbial hare on speed.

Bye, Alex
 

SilverbladeTE

Senior Member
Messages
3,043
Location
Somewhere near Glasgow, Scotland
If XMRV from infected labs does get to infect people, it could produce major problems years down the track. I wouldn't expect to see it produce major problems quickly - the incubation period would make HIV look like the proverbial hare on speed.

Bye, Alex

"The slow blade penetrates the shield" ;)
or, for those less familiar with classic scifi and a different take on this:
it's a case of the proverbial frog being slowly boiled and doesn't notice until too late.
Or...
a snowball rolling down a mountian, turning into an avalanche.
Or all three!

People have an amazing ability to block out the "unspeakable truth", the fact the living on a major fault line is gawd damn stupid, etc etc.
"Tokyo due a big one!" headline other day in soem news/science sites: wow, no one reads bloody history? Kanto, 1923. Plus of course, fact the city sits on top of FOUR bloody enormous faults. Tokyo is like building a barbeque next to a petrol station :p
What was interesting about that catastrophy back then was the firestorms did most of the damage, ie, it's not always the obvious threat that results in disaster, but how things can conspire, syngergize, surprise or snowball, or Human deliberate stupidity makes it worse (in that case, fire safety was "too much of a costly problem" etc).

For an infectious disease example of my convulted discourse...see drug resistant Tuberculosis.
Being greedy,stupid, deliberatley ignoring a problem can result on a catastrophic DISASTER, in years to come.
http://www.bbc.co.uk/news/health-16592199

Personally, I ponder whether we're going to make ourselves extinct with this crap?
"Screwing with the Human Genome, just say NO!" :D


doomed.jpg
 

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