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Raltegravir exacerbates mice autoimmune disease; might rule out use in treating CFS.

Discussion in 'XMRV Research and Replication Studies' started by leelaplay, Apr 5, 2010.

  1. leelaplay

    leelaplay member

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    kelly posted this reminder (from Nov 09) to CO-CURE today

    [Note: The PLos study regarding the implications of anti-viral use, should
    XMRV be proven pathogenic in humans, also brings up an immune issue found
    with one of the drugs studied which was published in late 2009.]

    Raltegravir inhibits murine leukemia virus: implications for chronic fatigue
    syndrome?


    by Vincent Racaniello on 20 November 2009

    [image: Raltegravir]The finding that a retrovirus, XMRV, is associated with
    chronic fatigue syndrome has lead to the suggestion that the disease might
    be treated with some of the antiviral drugs used to treat AIDS. The
    integrase inhibitor Raltegravir has been found to block the replication of
    murine leukemia virus, which is highly related to XMRV. But the drug
    exacerbates autoimmune disease in mice which might rule out its use in
    treating CFS.


    Retroviruses such as XMVR and HIV-1 have genomes composed of single-stranded
    RNA. This nucleic acid is converted to a DNA copy in infected cells by the
    viral enzyme reverse transcriptase. The double-stranded viral DNA is then
    integrated into the chromosomal DNA of the host cell, a process accomplished
    by an viral enzyme called integrase (illustrated).

    [image: retroviral_integration]

    Raltegravir (pictured above left) is an inhibitor of HIV-1 integrase that
    was approved for use in humans in 2007. The drug blocks the integration of
    viral DNA into the host genome and therefore inhibits viral replication.

    The mouse retrovirus murine leukemia virus (MLV) has been linked to the
    development of spontaneous autoimmune disease. The mechanism by which the
    virus induces this disease is not known, but stimulation of innate immune
    responses <http://www.virology.ws/2009/06/03/innate-immune-defenses/> by
    viral DNA might be involved.

    Raltegravir also inhibits integration of MLV DNA into the murine genome.
    When mice with autoimmune disease were treated with raltegravir, they
    succumbed to autoimmune disease a month earlier than untreated animals. Mice
    without the disease were not affected by the antiviral drug. The authors
    speculate that by inhibiting viral DNA integration, raltegravir increases
    the amount of unintegrated viral DNA, elevating innate responses and
    exacerbating autoimmunity.


    Its not known if raltegravir is active against XMRV, the retrovirus
    associated with chronic fatigue syndrome. Given the similarity between the
    genomes of MLV and XMRV it seems likely that the drug will inhibit the
    virus. If the ability of raltegravir to treat CFS is tested in clinical
    trials, it will be important to carefully monitor treated patients for signs
    of autoimmunity. CFS has an autoimmune component which could worsen with
    raltegrivir treatment.

    An obvious question is whether raltegrivir induces autoimmunity in AIDS
    patients. Im not aware of any such reports, which is probably not
    surprising given the fact that HIV-1 infection leads to immunosuppression.

    CFS sufferers should not despair: other antiretroviral drugs, including
    chain terminators such as AZT, do not allow the accumulation of unintegrated
    viral DNA. These compounds might be useful for treating the disease.

    G.B. Beck-Engeser, D. Eilat, T. Harrer, H.-M. Jack, M. Wabl (2009). Early
    onset of autoimmune disease by the retroviral integrase inhibitor
    raltegravir Proceedings of the National Academy of Sciences :
    10.1073/pnas.0908074106<http://www.virology.ws/2009/11/20/raltegravir-inhibits-murine-leukemia-virus-implications-for-chronic-fatigue-syndrome/10.1073/pnas.0908074106>


    --
    I learned very early the difference between knowing the name of something
    and knowing something.

    Richard Feynman The Physics Teacher Vol. 7, issue 6 (1969)

    -
     
  2. Hope123

    Hope123 Senior Member

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    Yeah, I had come across this a while back but I thought the fact that they used mice specifically created with an autoimmune disease already made a difference in how these results came out. Mice without an autoimmune disease did not have these issues. I also read somewhere else (can't find it now) that the drug might actually help certain autoimmune illnesses but not others.
     
  3. usedtobeperkytina

    usedtobeperkytina Senior Member

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    Clay, Alabama
    I would love to hear Klimas' reaction to this. She knows immune system best.

    Think this very issue reflects the circular nature of our immune system trying to recover from infection. Whether helped by retrovirus or just natural defense.

    Tina
     
  4. acer2000

    acer2000 Senior Member

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    Does it cause autoimmune disease in humans with HIV that take it? Or has it not been out long enough to tell?
     
  5. cfs since 1998

    cfs since 1998

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    Vincent Racaniello claims CFS "has an autoimmune component" but I have not seen any evidence of that. It seems autoimmune conditions are more common in CFS but I don't think it is an autoimmune disease in and of itself. I do not have any autoimmune issues. Also it says "exacerbates" autoimmune disease; that's a bit different from causing one where there wasn't before.
     

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