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Human APOBEC3 proteins can inhibit XMRV

Discussion in 'XMRV Research and Replication Studies' started by Jemal, Dec 8, 2010.

  1. Jemal

    Jemal Senior Member

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    Is this new? Publication date is 3 dec.

    http://www.ncbi.nlm.nih.gov/pubmed/21131013

    The last sentence doesn't really sound hopeful...

    It's going to appear in Virology.
  2. Jemal

    Jemal Senior Member

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  3. alex3619

    alex3619 Senior Member

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    Hi Jemal, the last sentence of the article you quoted says, in a nutshell, that either we rarely have XMRV or that we only have it in selected tissues. Given we know it has tissue specificity from the animal studies, this is not a surprise. Also APOBEC3 is likely to be one of the reasons this virus is so hard to find in blood. This does not mean we don't have XMRV, it means if we have it we aren't entirely defenseless. It might however explain why XMRV transmission rates are so low - most people probably fight it off, most of the time. However, I worry that the prevalence is so high that even if somebody fights it off 99% of the time, the number of times they have to do this is growing so huge that in time everyone who has no genetic immunity will catch it.

    Of course all this is tentative pending better research. Bye, Alex
  4. natasa778

    natasa778 Senior Member

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    They forgot to mention that MulVs have a way of inactivating human APOBEC3 !!

    (It makes sense that this would happen only after a certain period and not be observable within a short study time)
  5. Cort

    Cort Phoenix Rising Founder

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    I don't think this is unexpected. The APOBEC 3G enzymes beats the heck out of XMRV. If its going to be doing damage it would seem that it would have to be doing it in cell without that enzyme. He says most cells have that enzyme...the question is which cells do not and where are they?
  6. alex3619

    alex3619 Senior Member

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    Hi Cort, this is a very important question you raise and will tell us which types of cancer we might get, which tissues to biopsy for testing, and where the virus is hiding (so we can target it properly). Bye, Alex
  7. urbantravels

    urbantravels disjecta membra

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    Ila Singh's going to tell us where the virus is hiding!
  8. August59

    August59 Daughters High School Graduation

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    I would think her autopsy study would reveal a few places it likes to hang out.
  9. SA2

    SA2

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    APOBEC3 and an XMRV drug

    It seems that an anti-XMRV drug based on APOBEC3 (either a mimic or APOBEC3 stimulant) would be very effective against XMRV and low toxicity (since the cells already use it naturally). I wonder if any of the XMRV drug researchers are looking into this.
  10. garcia

    garcia Aristocrat Extraordinaire

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    I believe interferon boosts APOBEC3, so interferon-boosters (such as cycloferon) would be one potential avenue to explore.
  11. Jemal

    Jemal Senior Member

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    Ha! I was already wondering where I could sign up for pills that stimulate APOBEC3 :D

    The question is though: is boosting effective for areas that lack this defensive protein?
  12. FunkOdyssey

    FunkOdyssey Senior Member

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    This is interesting: from some very preliminary research, interferon-alpha is the primary interferon inducer of APOBEC3, not interferon-gamma. Yet immunovir helps many patients, and it does not seem to boost IFN-alpha (only IFN-gamma). Maybe it helps control the secondary infections or hits XMRV from another angle.

    Cycloferon DOES increase interferon-alpha production, so that is sounding increasingly promising.
  13. FunkOdyssey

    FunkOdyssey Senior Member

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    IL-2 seems to be important for APOBEC3G production as well. See:

    Quantitative profiling of the full APOBEC3 mRNA repertoire in lymphocytes and tissues: implications for HIV-1 restriction

    Maybe that's how immunovir helps.
  14. Cort

    Cort Phoenix Rising Founder

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    Actually I don't think we need to boost APOBEC 3 production - I think that enzyme is doing fine to keep the virus from replicating...(If it can do its damage without replicating - that's another story). What researchers will need to find is how to keep it down in cells that are missing that enzyme......
  15. urbantravels

    urbantravels disjecta membra

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    I haven't been able to figure out which cells or tissues that is. Anyone??
  16. Jemal

    Jemal Senior Member

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    I find it all very complicated. I have seen APOBEC3 be called an enzym, protein and even a gene. Humans seem to have 7 different families of the APOBEC3 gene. People that have a couple of active APOBEC3 genes seem to be completely immune to HIV infection. HIV has a trick of its own though, it uses a special protein to inactivate APOBEC3. XMRV doesn't know this trick (yet). HIV doesn't always use this trick though, so some people are truly immune to HIV.

    It's maddingly difficult to understand... I am guessing at least part of the answer can be found in this study:
    http://www.ncbi.nlm.nih.gov/pubmed/19587057
  17. SA2

    SA2

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    Developing an APOBEC3 mimic could help. The other alternative is to find a drug that can activate the APOBEC3 gene(s) in those cells that don't express the gene(s). Such a drug might help prevent/treat HIV infection as well. If there are multiple varieties of the APOBEC3 gene in most people with most of them inactive, then activating some or all of the varieties (especially in those cells with the least expression) may provide a very effective treatment for XMRV, HIV, and perhaps all forms of human retroviruses.
  18. garcia

    garcia Aristocrat Extraordinaire

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    I'm not sure that is always the case.

    For example see here:

    Source: http://jvi.asm.org/cgi/content/abstract/84/20/10933

    [Thanks to Sunshine for finding the above reference]
  19. Daffodil

    Daffodil Senior Member

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    doesn't vif inhibit HIV? doesnt seem do much for people with that!
  20. alex3619

    alex3619 Senior Member

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    Hi Jemal, maybe this will help. Nearly all enzymes are proteins. All proteins are directly or indirectly made using a gene (via a step involving RNA). So APOBEC3 is most specifically an enzyme unless you are talking about its genetics in which case talking about a gene is more appropriate.
    Bye, Alex

    ps I hope I am not oversimplifying and stating the obvious because you needed to vent

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