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XMRV: exogenous and/or endogenous?

Discussion in 'XMRV Research and Replication Studies' started by fresh_eyes, Nov 12, 2009.

  1. SeaShel

    SeaShel Senior Member

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    Thanks for posting this fresh eyes.

    I'm currently in an HERV K18 study Dr. Huber is doing.

    I don't know anything about scientific method and studies, but when the XMRV news broke I wondered if they would test the study participants "on the side" for XMRV.

    Your explaining the exo and endo helped me have the correct words for what I was thinking.

    Since she was quoted in this article, I'm even more curious to know what might be going on behind the scenes. I haven't had a definitive answer from the research aide as to whether will be given any info on our specific samples.

    Shelley
  2. shrewsbury

    shrewsbury member

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    How interesting Mark. Is this Mark, ex- angry old man and now x? ?

    It's tough for me to follow the science. Would this be a fair extrapolation - if the human race has manged to turn exogenous retroviruses into endogenous, then there should be antibodies or whatever mechanisms that work with retroviruses in our cells as well that will re-turn off the old endogenous retroviruses? So this would be an avenue for research for a cure?

    Could one use an analogy that the 8% of the genome that are old endogenous retroviruses are like a vaccine. It's how the body immunizes itself against them. Somehow xmrv is activating the "vaccine" (viruses that the body has kept to prevent being vulnerable to them) so that the vaccine is causing disease rather than preventing it.

    Thanks to all who help me try to follow this!

    islandfinn
  3. Mark

    Mark Acting CEO

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    That's me. Further changes of identity would not be out of character...

    I immediately suspected something similar when I read about the 8% of the genome that's ancient retroviruses. The other thread relevant, I think, posed the question as to whether retroviruses are what drive evolution, which also raises fascinating questions.

    As a computer programmer, I instinctively thought of the 8% as effectively functioning as a kind of memory bank of old infections. On the one hand, the story is that retroviruses inflitrate the immune system and eventually survive as endogenous DNA code, and I then imagine that evolutionary pressure, and some other mechanism, eventually combine to 'switch off' any harmful endogenous code in the human genome. But on the other hand, it's interesting that the deactivated code remains in the genome: is it put to any use?

    Of course one can easily imagine why the body might have no mechanism for getting rid of such bits of code in its DNA, but I would tend to suspect that in evolution, nothing is wasted, and this bank of information could feasibly be very useful to the immune system. As an idea of the type of thing: is it possible that the immune system consults this bank of ancient retroviruses when it encounters a new molecule for the first time and has to decide whether to create antibodies for it or not? Something along those lines.

    I suspect it would be a bad idea to describe the bank of information as a "natural vaccine" though, and I don't think any of this theory we're speculating over is necessary to explain why infections and/or vaccines can trigger a response from XMRV. The explanation that part of the immune system is corrupt because XMRV has overwritten some of its code and co-opted some of the immune mechanisms, seems quite sufficient to explain the effects we're considering, without needing to bring re-activation of endogenous retroviruses into play.

    The whole question is more likely to have deep implications for the understanding of older diseases rather than for new ideopathic conditions. I've suspected for ages that when they eventually crack our condition they will unlock whole new areas of medical science in the process, and all this new science I'm reading about sounds as if it has the potential to do exactly that.
  4. _Kim_

    _Kim_ Guest

  5. shrewsbury

    shrewsbury member

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    what fun!

    Or maybe it's like quarrantine with computer virus checks? Aren't those saved but locked away. Being a computer-guy, you would better know if the anaology works.

    I agree. I had a niggly feeling as I wrote that. I think 'vaccine' is one of those trigger words now that people bring a history to that might obsfucate the meaning here. Wrong choice of words.

    if:)
  6. Mark

    Mark Acting CEO

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  7. Mark

    Mark Acting CEO

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    Yes, that was it! That's a much better expression of how I saw it: Quarantine. If an ancient retrovirus comes back round again, it's filed in the genome under "harmful: deactivated" - that surely must be useable information, at least to identify retroviral patterns when they are encountered.
  8. fresh_eyes

    fresh_eyes happy to be here

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    I agree, Mark x. Years ago I heard a doctor say the same thing, and it's always stuck with me. Amazing that it seems it might be happening now.

    ps Thanks so much for posting the MS info - I'll read it when the brain fog clears.
  9. fresh_eyes

    fresh_eyes happy to be here

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    This is so interesting, SeaShel. So, you don't know your test results re HERV K18? How did you get in the study? Is it all people with ME/CFS?
  10. SeaShel

    SeaShel Senior Member

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    fresh eyes, I'm glad you asked! I had typed out 3 paragraphs of an answer and decided to dig up the study paperwork I received originally to more completely answer you, and found out the the answer to a question I had only guessed at. (was that clear as mud?)

    I honestly don't remember where/how I heard about the study, but have to think it was from the ProHealth board. I've been sick so long that I had gone for quite some time without keeping up on much and only visiting that board very infrequently, as it was just too discouraging not having a good doc and not much new to go on.

    The study is "HERV K18 as a Risk Factor for CFIDS" and the docs are Renee Taylor of U of Illinois at Chicago, Brigitte Huber of Tufts, Ben Katz of Children's Memorial Hospital in Chicago, Andrew Lloyd of U of New South Wales. It's supported by the NIH.

    Anyway, I will just quote from my paperwork for you:

    "Previous studies have found a conection between having mono or an HHV-6 (roseola or sixth disease) infection and CFS. There may be a genetic link that explains this connection. The purpose of this study is to test whether some people with CFS carry a gene that would make them more likely to have CFS after having mono or an HHV-6 infection."

    Further on it says:

    ....if you meet certain conditions, you will be invited to participate in Phase II of the study. Eligibility to participate in Phase II will be based on 2 criteria:.....you are not in remission and your symptoms are active and severe; and if the results from the first blood draw indicate that you have the specific genetic makeup for the CFS that we are studying (variation in the HERV K18 gene), then we will invite you to participate in the second phase of the study.

    I've had 2 draws and at the 2nd interview it was said I'd be continuing on, but I'm not taking that as cast in stone till I get something official.

    It sure wouldn't break my heart to have them test for XMRV also, and share their findings.

    I wonder if this will shift anything with the study, or is that a total no-no?

    Let me know if there's anything else you'd like to know.
  11. fresh_eyes

    fresh_eyes happy to be here

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    Wow, SeaShel, that is so interesting. I had not been keeping up with CFS research until XMRV (like you, I found the whole topic kind of discouraging) and I had never thought that "genetic predisposition to CFS" could mean something to do with endogenous retroviruses. I guess that sheds some light on the question asked earlier re: do we all have the exact same ones - there are clearly some differences.

    I'm pretty sure that's a total no-no, but I'm sure it is influencing what they want to do next - maybe they'll design a followup XMRV study using the same samples. I do hope you'll keep us posted.
  12. SeaShel

    SeaShel Senior Member

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    Absolutely, I will keep you posted. It's probably yet another situation of 'hurry up and wait'. I don't expect to hear anything about the next round till March or April.

    With my inherent lack of patience and nosy nature, if I was a researcher on this study you can bet I'd be running the samples for XMRV as soon as I could though. :cool:

    Shelley
  13. Advocate

    Advocate Senior Member

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    On the endogenous/exogenous question, here's something that was posted yesterday on the National Cancer Institute website, in a Q and A:

    http://www.cancer.gov/newscenter/pressreleases/XMRV_QandA
  14. fresh_eyes

    fresh_eyes happy to be here

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    Also on the endo/exo question, I re-watched Coffin's CFSAC testimony today, and he said that the MLV that is the very close relative of XMRV (what the M stands for) is eNDogenous. In mice. I don't know if anybody else missed that the first time, but I did.
  15. George

    George Guest

    XMRV can only be Exogenous = from without

    If I understand what you concerned about it's the transmission of the virus. I wanted to make sure that people don't use the word incorrectly especially with the doctors who can be pains about the smallest things. (big grin) You may have noted on the interview with Dr. Kilamas that she pointed out this virus is most likely handed down from parents to children. That doesn't make it Endogenous though. In order for a virus to be classed as Endogenous it has to be part of the total genome. Not just part of the DNA in a couple of thousand cells.

    What is being passed down from parent to child is live virus. Eventually virus passed from mother to child in the womb will begin to create immunities and after around a 100 generations or so the immunity will be integrated into our total DNA.

    The test is does it cause problems in the host it's infecting. If it does then it's still Exogenous. XMRV causes problems in humans, therefore it is exogenous or from without. Even if it is passed down five generations, which is about right with XMRV.

    It will only become endogenous when it becomes a part of the human genome rather than just infecting the DNA of a specific cell. As a part of the human genome it would mean that it would no longer cause problems, we would have integrated it into our DNA. Kind of like Neiman pic. It's part of our gene structure but in general it doesn't cause problems unless there is a genetic defect at conception.

    SIV jumped species to become HIV. SIV in monkeys is not a problem for the monkey but HIV reinserted into a monkey causes problems. And of course to humans as well because they have no immunity to the HIV virus. MLV doesn't bother mice it's part of their make up. Except when humans take it out of their genetic structure, change it (into say MLV-6) and put it back into the mice. Then it wreaks havoc because the mice have no Endogenous immunity to the changed virus RNA.

    Every few thousand years Humans get hit with something like this. Over the course of 50,000 years we have weathered a lot of virus that have jumped species. That's why a portion (about 8%) is incorporated into our DNA. We get hit, we have people who build immunity, we incorporate it so that it become Endogenous, then the virus in question isn't a problem any more.

    Happily in our lifetimes we have drugs!:D:D:D
  16. Alice Band

    Alice Band PWME - ME by Ramsay

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    Prevalence of Chronic Fatigue Syndrome and Chronic Fatigue Within Families
    of CFS Patients

    Journal: Journal of Chronic Fatigue Syndrome (ISSN: 1057-3321), Volume: 13
    Issue: 1 Page Range: 3-13 [2006]

    Authors: Rosemary A. Underhill MB, BS, MRCOG, FRCSE, Ruth L. O'Gorman

    The prevalence of CFS (Chronic Fatigue Syndrome) and chronic fatigue were
    investigated in family members of CFS patients using a questionnaire-based
    study.

    Significant differences were seen between the prevalence of CFS in all
    groups of family members relative to the published community prevalence
    of 0.422%, (spouses/partners: 3.2%, p < 0.001; offspring: 5.1%,
    p < .001; parents and siblings: 1.1%, p < 0.02; second and third degree
    blood relatives 0.8%, p < 0.02.)

    The prevalence of CFS was higher in genetically unrelated household
    contacts and in nonresident genetic relatives than in the community,
    indicating that both household contact and genetic relationship are risk
    factors for CFS.
  17. Marylib

    Marylib Senior Member

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    You guys are smart

    I am waiting for the "dummies" version of this;)
  18. fresh_eyes

    fresh_eyes happy to be here

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    Hi George. Thanks for your very lucid explanation about endo vs. exo. That fits with understanding as well, though I suspect there may be more yet undiscovered in that field. One question, though - how does your explanation fit with the quote from the top of the thread:

    "This new retrovirus [XMRV] may be able, through infecting human cells, [to] induce a transcription of an endogenous virus," says Huber, who has been studying the presence of an ancient retrovirus (HERV-K18) dormant in most people but active in patients with CFS and multiple sclerosis. "We've already shown that Epstein-Barr virus can do exactly this."

    (The complete article goes into it more: http://www.scientificamerican.com/article.cfm?id=chronic-fatigue-syndrome-retrovirus)

    My understanding of this was that EBV has been shown to re-activate the endogenous "ancient retrovirus HERV K-18", and they wonder if that reactivated retrovirus then begins to "cause problems" again, at least in combination with the EBV (or maybe XMRV). Or no? I thought that was the point of that research.
  19. Mark

    Mark Acting CEO

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    Wow this simple question is proving to be a tough one to pin down!

    What George said makes sense, but how does it square with the quote Advocate picked out from the NCI Q&A?

    ""When retroviruses infect germ cells (sperm or egg), endogenous viruses, can develop. The integrated viral DNA, or provirus, is passed from parent to offspring. There is no evidence suggesting that XMRV can do this in humans."

    I read that as saying that if XMRV were to infect a germ cell, that could put it in the DNA of offspring and result in an endogenous virus. The only way I can square that with George's post is if, when they say "can develop" they mean "can develop 100 generations later", but that seems a bit of a stretch.
  20. fresh_eyes

    fresh_eyes happy to be here

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    Good point, Mark. It has turned out to be a very complex question, hasn't it?

    George, what would be happening in the mean time, between that first germ-cell infection and fully defunct endogenous status generations later? Wouldn't it be getting passed down in some people's germ cells (& perhaps causing disease) for some time before that immunity you describe developed? Wouldn't it be "endogenous" in some people during that time - or is it only endogenous when the entire human race has it in their genome? Do we all have all the same endogenous retroviruses?

    My questions have only increased since hearing Klimas' statement that they think XMRV is likely passed down mother>child or father>child. Obviously, unless we're talking about the germ cell (sperm) being infected, father>child wouldn't really come into play - it would just be father>mother>child, which is totally different.

    And thanks for sharing your knowledge, George - do you have a background in this kind of thing?

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