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Anti-HIV drugs AZT, tenofovir, and raltegravir may be useful for treatment of XMRV

Discussion in 'XMRV Research and Replication Studies' started by redo, Jun 1, 2010.

  1. redo

    redo Senior Member

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    A new study has been published:

    http://www.ncbi.nlm.nih.gov/pubmed/20335265

    Inhibition of xenotropic murine leukemia virus-related virus by APOBEC3 proteins and antiviral drugs.

    Abstract:
    Xenotropic murine leukemia virus-related virus (XMRV), a gammaretrovirus, has been isolated from human prostate cancer tissue and from activated CD4(+) T cells and B cells of patients with chronic fatigue syndrome, suggesting an association between XMRV infection and these two diseases. Since APOBEC3G (A3G) and APOBEC3F (A3F), which are potent inhibitors of murine leukemia virus and Vif-deficient human immunodeficiency virus type 1 (HIV-1), are expressed in human CD4(+) T cells and B cells, we sought to determine how XMRV evades suppression of replication by APOBEC3 proteins. We found that expression of A3G, A3F, or murine A3 in virus-producing cells resulted in their virion incorporation, inhibition of XMRV replication, and G-to-A hypermutation of the viral DNA with all three APOBEC3 proteins. Quantitation of A3G and A3F mRNAs indicated that, compared to the human T-cell lines CEM and H9, prostate cell lines LNCaP and DU145 exhibited 50% lower A3F mRNA levels, whereas A3G expression in 22Rv1, LNCaP, and DU145 cells was nearly undetectable. XMRV proviral genomes in LNCaP and DU145 cells were hypermutated at low frequency with mutation patterns consistent with A3F activity. XMRV proviral genomes were extensively hypermutated upon replication in A3G/A3F-positive T cells (CEM and H9), but not in A3G/A3F-negative cells (CEM-SS). We also observed that XMRV replication was susceptible to the nucleoside reverse transcriptase (RT) inhibitors zidovudine (AZT) and tenofovir and the integrase inhibitor raltegravir. In summary, the establishment of XMRV infection in patients may be dependent on infection of A3G/A3F-deficient cells, and cells expressing low levels of A3G/A3F, such as prostate cancer cells, may be ideal producers of infectious XMRV. Furthermore, the anti-HIV-1 drugs AZT, tenofovir, and raltegravir may be useful for treatment of XMRV infection.

    PMID: 20335265 [PubMed - in process]

    Study is by: Paprotka T, Venkatachari NJ, Chaipan C, Burdick R, Delviks-Frankenberry KA, Hu WS, Pathak VK.
     
  2. redo

    redo Senior Member

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    I know this is in vitro, but none the less, I think that when they find that the drugs work against XMRV, and several of those who use the drugs react to them (both getting better and worse), it's a strong indication we're on to something.
     
  3. hvs

    hvs Senior Member

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    Wow, serious research in a huge impact-factor journal. The medical science research is running way ahead of the research on whether xmrv is causative for "cfs". I wonder when we'll have clinical studies of "cfs" patients on anti-retrovirals. I reckon it will take such studies showing people getting better before the causative relationship is accepted by a medical community habituated to misunderstanding this disease.
     
  4. garcia

    garcia Aristocrat Extraordinaire

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    London, UK
    NCI-frederick is John Coffin country. Dem some serious retrovirologists!
     
  5. Rrrr

    Rrrr Senior Member

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    is this new news? i thought the singh (sp?) study already said all this about these hiv drugs inhibiting xmrv in vitro... is this just a confirmation of that info from another study?
     
  6. Daffodil

    Daffodil Senior Member

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    so we will have to deal with all the same things HIV patients deal with like chronic inflammation, lypodytrophy, etc etc right?
     
  7. julius

    julius Watchoo lookin' at?

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    Canada
    So, is it possible then that CFS affects levels of A3, which allows XMRV to replicate freely. Thus making XMRV an opportunistic infection, rather than the cause of CFS?
     
  8. hvs

    hvs Senior Member

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    I've never seen this distinction as significant as I'd be shocked if treating the XMRV regardless of whether the "real" cause is genetic, etc. etc. doesn't fix the patient.
     
  9. cfs since 1998

    cfs since 1998 *****

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    No, this study was epub in March and actually predates the Singh results.
     

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