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Discussion in 'Media, Interviews, Blogs, Talks, Events about XMRV' started by shannah, Oct 18, 2010.

  1. Jemal

    Jemal Senior Member

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    I think I read somewhere they found variants of the virus that might still be able to infect both humans and mice?
     
  2. urbantravels

    urbantravels disjecta membra

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    HTLV prevalence in the US is vanishingly small, that's probably why stats aren't easy to find.
     
  3. Otis

    Otis Señor Mumbler

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  4. eric_s

    eric_s Senior Member

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    Thanks. But are you sure, we are not having a misunderstanding? I was asking about the study where Cooperative Diagnostics was involved, not the Lombardi et al. Science paper. I think that one was first published on Oct 8th in Science Express.
     
  5. Bob

    Bob

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    XMRV is purely a human virus, as per as our current knowledge, and it has never been found in mice, so far.
    The confusion about whether XMRV is a mouse virus or a human virus arises because XMRV is very similar to MLV's, which are mouse retroviruses.
    The similarity to MLV's is where the name comes from:

    X - Xenotropic
    M - MLV
    R - Related
    V - virus

    (i.e. XMRV is an MLV-related virus) (So it is related to MLV's but it is not an MLV itself.)

    Another reason for some of the confusion is the use of the 'X' or 'Xenotropic'.

    'Xenotropic' indicates that a virus can infect, and replicate in, another species (i.e. in this case, humans.) other than the original host species (i.e. mice), but that it cannot infect, or replicate in, the original host species (i.e. mice).
    But in the case of XMRV, 'X' (xenotropic) is referring to behaviour of the mouse viruses (MLV's) that XMRV is similar to... The 'X' is not referring to the behaviour of the new human virus 'XMRV'.
    So, in other words, the X-type MLV's, that XMRV is similar to, can infect other species other than the original mouse host, but they cannot infect, or replicate in, mice.

    So a question arises: "how can a mouse virus exist in the first place if it cannot infect or replicate in any mice?".
    This is where it gets even more confusing!
    'X' type MLV's (Xenotropic MLV's) are 'endogenous' retroviruses. An endogenous virus is not an independent virus, but exists as part of the host species' DNA. Evolutionary process have meant that a retrovirus managed to insert it's own DNA into the mouse DNA (retroviruses replicate by inserting themselves into the host species' own DNA) and it has then entered the germ-line cells (sperm and egg cells), and the virus DNA has been passed into the DNA of every cell of the next generation of mice... Over time, this has become widespread through out the whole of the species.

    So, endogenous retroviruses are encoded in the host species' DNA.
    It is possible to check to see if PMRV or XMRV are lab contaminants from either mouse DNA, or endogenous mouse retroviruses, by checking the genome of PMRV or XMRV against the mouse genome. If PMRV or XMRV were found to be encoded in mouse DNA, then their discovery might have been due to mouse contaminants, but they aren't encoded, and, anyway, there are many other reasons why XMRV and PMRV have been shown not to be contaminants.

    The reason that mice can't be infected with their own endogenous X-type viruses is that they have evolved an immunity to the virus. However, the endogenous viruses can still encode for viral particles and proteins, but they can't form whole, replicating viruses in the host mouse species. It is possible for these viral particles and proteins to jump species, however, where they can then become active viral particles, combine, and form whole, replicating, viruses in the new host species. (i.e. viral particles can jump species where they can then become whole viruses.) If the mice were to lose their genetic immunity to their own endogenous retroviruses (retroviruses encoded in their own DNA), then the mouse's own DNA could theoretically start encoding and forming whole retroviruses because there would then be no immune process inhibited the forming of whole viruses.

    The 'X' in 'XMRV' refers to a type of MLV virus (X-MLV) that was already known to science. However, it seems that the 'X' is now a loose term because, since the naming of X-MLV's, more research has been carried out which demonstrates that these viruses behave differently in different strains of mice. Some strains of mice are susceptible to infection by X-type (xenotropic) MLV's. So it seems that 'X' has become purely a name rather than an indicator of function. Indeed XMRV also has P-type MLV genetic code in it anyway. 'P' indicates polytropic virus behaviour which means that the virus can infect and replicate in the original host species as well as being able to jump to a new species.

    We hardly know anything at all about XMRV yet and it's helpful to know as much as we can about it, including whether it is purely a human virus, or a cross-species mouse virus. Knowing for certain that the virus is not present in any mice also helps to prove that XMRV is not a lab contaminant originating from mice.

    We can't be 100% certain that XMRV is not harboured by any mice because there are so many different varieties and populations of mice in the world, including wild and domestic and lab mice. This means that certain strains of mice are susceptible to different viruses, and diverse mice populations might be exposed to, and harbour, different pathogens.

    XMRV has never been found in mice, but it is similar to mouse viruses, so it is possible that XMRV might be hiding in some small mouse population, somewhere. However, at the moment, it looks like XMRV is purely a human virus which probably originated in mice... If this is the case then a mouse virus would have crossed over to the human species at some point in our history, and then the virus would have mutated so that it easily passes from human to human, and easily replicates in humans. When it mutated, it became purely a human virus, as long as it is not passed back to the mouse population. If it is found in the mouse population then it will be a cross-species virus.

    Mouse DNA includes the DNA of endogenous mouse viruses (MLV's) which is why alter checked the genome of his PMRV's against the mouse genome, to see if the PMRV's he detected could be due to contamination from mouse MLV's (endogenous mouse viruses) or mouse DNA. He didn't detect any of the mouse genome in his PMRV's.

    One other thing to mention (thanks to anciendaze for pointing this out) is that there could be an intermediate species, between mice and humans, where XMRV originates from. In other words, an MLV could have jumped to another animal species, from mice, where it then mutated into XMRV. And then XMRV could have jumped to humans from the intermediate species.

    This subject is extremely confusing, and I know I haven't written this very clearly (writing clearly doesn't come easily to me)... But I hope it helps...
    I can't guarantee that I'm 100% accurate with everything because I'm not an expert in mouse virology! But I think it's all accurate, after having done some heavy-duty reading about it all.
     
  6. Sasha

    Sasha Fine, thank you

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    Thanks, Bob! That's very a very clear explanation. Thanks for putting the time and effort into explaining!
     
  7. anciendaze

    anciendaze Senior Member

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    To clarify one point in Bob's discussion, we have so far only found XMRV "in the wild" in humans. This need not imply it originated there. We already know it can infect several other species. The change from ecotropic or polytropic to xenotropic could have taken place in an unknown intermediate vector. We probably wouldn't notice until it infected humans.

    The variety of tropical rodents is astonishing. A huge previously-unknown species was found in the last few years. Fortunately, this was considerably smaller than the largest fossil rodents.
     
  8. Bob

    Bob

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    Thanks Sasha.

    Thanks anciendaze... I keep forgetting that there could be an intermediate species...
    Hope you don't mind, I've added your point onto my post, in case anyone copies and pastes what i've written.
     
  9. Cort

    Cort Phoenix Rising Founder

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    I think that says it all Bob - well done! That cleared up some things for me.
     
  10. Jemal

    Jemal Senior Member

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    Yeah, thanks Bob. For someone stating that writing doesn't come easy you have done one heck of a job :)
     
  11. Otis

    Otis Señor Mumbler

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    I agree. Maybe we can find this a home for future reference rather than buried in this thread - maybe on the wiki?
     
  12. Bob

    Bob

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    Well, I'm totally flattered by all your comments... thanks everyone.

    Otis, please feel free to repost it anywhere if you think it would be helpful... Or i could post it as a blog?
     
  13. Jim

    Jim Senior Member

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    so how could the wpi/nci/cc test results be contaminated if no known mice can carry xmrv? would it have to be from some untested mice that can carry it? or could contamination come from some other source?
     
  14. alex3619

    alex3619 Senior Member

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    Hi Jim, One species of mouse can carry XMRV that we know of, but it would not be a typical lab mouse. Seventy types of mice have now been tested and found negative for XMRV. Of course, the naysayers may just claim it was some other mouse strain, maybe in a lab that later made some of the material used in PCR, blood collection etc. It still doesn't explain antibodies, but that could be just chance. It also doesn't explain viral budding under the electron microscope, but that could have been another virus. It also doesn't explain transmission of the virus, but hey, if you have a contaminating virus couldn't it be transfered? Then there is the problem that controls have a much lower prevalence of XMRV, but hey, maybe the used a different technique or materials? Oh yes, and the virus must be evading testing for mouse DNA because it didn't come directly from a mouse, its been in the lab for a long time.

    So to claim viral contamination you have to believe in every one of the following:

    1. A strain of mouse that could carry XMRV, which is rare at best, was used in a lab a long time ago, somehow got XMRV, and contaminated the lab which went on to make testing materials that were widely distributed everywhere.

    2. We have some other either XMRV or some other virus that is causing budding - due to contamination from #1 above if XMRV.

    3. We have antibodies to some other virus - they aren't XMRV antibodies, but share some features, with enough epitope similarity to cross react.

    4. Following #1, the viral contaminant moved on to infect a new sample. I mean, it has to be contaminating samples somehow.

    5. Since the contaminant came from other contaminated materials, and the virus must be replicating, there is no trace of the original mouse DNA.

    These are, in combination, very unlikely, but number six kills this hypothesis without extraordinary evidence, which nobody has supplied:

    6. Somehow the test samples have lots of contaminant, consistently in many labs; but this only happens rarely to controls, consistently in many labs.

    What you are left with is that for this idea to be plausible it would have to be a deliberate contamination i.e. scientific fraud. I don't think the naysayers would dare to go that far. It would also take a James Bond of the Science Fraud Division to contaminate that many samples at that many places. Hmmmmm ... maybe the British? (Just joking :))

    Bye
    Alex
     
  15. Bob

    Bob

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    For clarity, XMRV hasn't been found in any mice, but researchers were able to infect some mice with XMRV in a lab...
    Is this what you mean Alex?
     
  16. anciendaze

    anciendaze Senior Member

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    This overlapped the post by alex3619.
    One of the remarkable things about those saying "contamination" is the extent to which they avoid explaining what they mean. Contamination by sequences derived from ERVs in mice could change some PCR results, but would not produce antibodies in humans. Contamination by actual virus could affect cultures, if you can find a source, but, again, contaminated cultures do not produce those antibodies in people. Contamination of one lab would not affect work done at several other labs the same way. You would not expect to find consistent differences between patients and healthy controls. Simultaneous contamination by multiple species of virus is unlikely. Mutation in long-term patients is not likely to be mimicked by laboratory contamination. Finally, the number of uncontaminated negative controls run through the same labs along with samples is now at least up in the hundreds.

    Try as I might, I can't make any scenario work. I suspect the word "contamination" is being used in place of "fraud", which few will suggest in public. If they did, Harvey Alter would not stay quiet long.
     
  17. alex3619

    alex3619 Senior Member

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    Hi Bob, Yes that is what I mean. If we can infect it, it can carry it, but that doesn't make it a lab mouse nor a natural source. Bye, Alex
    PS anciendaze, I agree completely, hence my James Bond comment - contamination doesn't fly as an explanation without extraordinary evidence, and none has been provided.
     
  18. Jim

    Jim Senior Member

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    so what kind of physical materials in testing did the 3 labs from the science paper have in common? and also by the hansen study? i don't know anything about what materials are used to test for xmrv, except perhaps what's in the test tubes at blood collection (e.g. not sure what primers and cell lines and assays and such really are).
     
  19. alex3619

    alex3619 Senior Member

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    Hi Jim, I have no idea but I bet the Blood Working Group does. We shall know soon I think, Bye, Alex.
     
  20. Sasha

    Sasha Fine, thank you

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    Is there a date for when the blood group reports? I think I saw some mention of "three weeks" a short while ago.
     

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