Cleaning up after XMRV

18 May 2012

XMRVThe retrovirus XMRV does not cause prostate cancer or chronic fatigue syndrome – that hypothesis was disproved by the finding that the virus was produced in the laboratory in the 1990s by passage of a prostate tumor in nude mice. A trio of new papers on the virus attempt to address questions about the serological detection of XMRV in prostate cancer, and further emphasize that XMRV is not a human pathogen.

Absence of XMRV and Closely Related Viruses in Primary Prostate Cancer Tissues Used to Derive the XMRV-Infected Cell Line 22Rv1. The human cell line 22Rv1, which was established from a human prostate tumor (CWR22), produces infectious XMRV. It was previously shown that DNA from various passages of the prostate tumor in nude mice (called xenografts), did not contain XMRV, but cells from the mice do contain two related proviruses called PreXMRV-1 and PreXMRV-2 which recombined to form XMRV between 1993-1996. In a new study samples of the original prostate tumor CWR22 were examined for the presence of XMRV or related viruses. PCR assays targeting the viral gag, pol, and env sequences failed to provide evidence of XMRV in CWR22 tissue. These assays could detect endogenous murine leukemia virus DNA in mouse DNA, indicating that the CWR22 tumor contained neither XMRV nor related viruses. In addition, no XMRV sequences were detected when sections from the CWR22 tumor were examined by in situ hybridization. The same assay previously detected XMRV sequences in stromal cells of prostate tumors. The authors conclude that “Our findings conclusively show an absence of XMRV or related viruses in prostate of patient CWR22, thereby strongly supporting a mouse origin of XMRV.”

An important question not addressed by this study is why XMRV was originally detected in multiple prostate tumors obtained from patients at the Cleveland Clinic. The authors seem to be working on this problem, as they state that “…the sequence of XMRV present in 22Rv1 cells is virtually identical with XMRV cloned using human prostate samples, thus suggesting laboratory contamination with XMRV nucleic acid from 22Rv1 cells as the source. Further experiments designed to confirm or refute this hypothesis are currently underway.”

No biological evidence of XMRV in blood or prostatic fluid from prostate cancer patients. Samples from individuals with prostate cancer were tested for the presence of infectious XMRV and for antibodies against the virus. Neither infectious virus nor antibodies were detected in blood plasma (n = 29) or prostate secretions (n = 5). Among these were five specimens that had previously tested positive for XMRV DNA, including two from the original study. The authors conclude that the results “support the conclusion from other studies that XMRV has not entered the human population”.

Susceptibility of human lymphoid tissue cultured ex vivo to Xenotropic murine leukemia virus-related virus (XMRV) infection. Although XMRV is not known to cause human disease, whether it has to potential to do so is unknown. The virus can infect a variety of cultured human cells including peripheral blood mononuclear cells and neuronal cells. In this study the authors placed human tonsillar tissue in culture and infected it with XMRV. Proviral (integrated) DNA could be detected in the cells several weeks after infection and virus particles were released into the medium. However these released viruses could not infect fresh tonsillar tissue, possibly due to modification by innate antiviral restriction factors such as APOBEC, which is known to inhibit XMRV infectivity.

Based on their findings the authors conclude that “laboratories working with XMRV producing cell lines should be aware of the potential biohazard risk of working with this replication-competent retrovirus”.

It is clear that XMRV does not cause chronic fatigue syndrome; the original findings of Lombardi and colleagues linking the virus to this disease have been retracted by the journal. However there are still two papers in the literature that report the presence of XMRV in prostate – the original XMRV discovery paper and one from Ila Singh’s laboratory. In both papers XMRV detection in tissues was accomplished by using serological procedures. Based on the papers summarized here, the assays did not detect XMRV – but a satisfactory explanation for the positive signals has not yet been provided.

  • Tony Mach

    Winston, do you want fake evidence for viruses in ME/CFS? Like in table 4 of the Addendum?
    http://parakoch.blogspot.com/2012/02/request-for-clarification-regarding-33.html

    But please tell me: What good is fake evidence for you?

  • Tony Mach

    What I find fascinating: Neither her defenders nor her critics have actually and fully read the works of Dr. Mikovits. What a shame. One can find such a beautiful gem if one looks into the table 4 of the Addendum alone:
    http://parakoch.blogspot.com/2012/02/request-for-clarification-regarding-33.html

    No question, the table 4 from the addendum is the result of fiction, because no matter how you try to spin the facts, table 4 is severely at odds with several statements of Dr. Mikovits. I would say table 4 was the result of fabrication.

    What other gems are there to find in Dr. Mikovits work, if one looks more closely?

    But why stop there? Nobody is talking about the contributions of Dr. Ruscetti. Such a shame. His report of the 100% peak shift, which is at odds with any imaginable pathologies of an hypothetical infection of humans with XMRV (and even at odds with infections of human cell lines with XMRV) would overturn large parts of virology. A virus at lower concentrations than HIV is capable to infect 100% of white blood cells. Must be some kind of homeopathic effect! Less viruses infect more cells! Surely, if this stands, there is at least one invitation from the Karolinska Institutet on its way to NCI Frederick! Not that the poor Ruscetti ends up the same way as poor Gallo – after all, their respective contributions to AIDS and to ME/CFS are on par.

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  • Guest1

     Dr Mikovits is gagged.  Dr Ruscetti is a Government employee. 

    The first is because of the Whittemore’s actions.

  • Guest1

     Tony one patient is not included in table 4, they are included in the other tables of that paper.

    You should have taken the time to read the paper before making that comment.

    Oh and the VP62 plasmid was NEVER in the WPI or NCI labs.  They never used it.  Get your facts right.

  • Guest1

    Tony were are you getting these ideas from? AZA does not have an affect on ERVs and is used to find latent HIV. 

  • Guest1

     Science had no reason to retract.  They have shown their true colours.

    The NIH study is a dud.  The have not used a recognized entry criteria for the study.  No point getting the Government to do any research.  We need independent scientists like Dr Ruscetti and Mikovits and Hanson. 

  • Guest1

    Then how do you justify the actions of every negative study which used assays that are not clinically validated and failured to replicate the proven methods from Lombardi et al.?

    Hanson again found the viruses.  That is 4 ME papers finding HGRVs.

  • Guest1

     Without reserach by scientists who have shown they are willing to practice science no patient is going to fall for that.  We need research NOW into the HGRVs that Mikovits and Ruscetti discovered!

  • Guest1

     The viruses Mikovits and Ruscetti discovered were not XMRV.  They were different HGRVs.  Everyone knows this. 

    Huber has problems with contamination.  A HERV cannot cause the results of the positive studies.  You cannot explain ME through HERVs.   

  • Guest1

     Nope, they have created a new criteria.  It is not a replication study and now the Government’s entire handling of this research is under scrutiny.  The viruses were never XMRV, but other HGRVs.

  • Guest1

     Are you a patients or a control and were you be included in the final set of results.  Do you have the Canadian criteria ME or are you a fatigue patient.  How were the samples collected and processed, how were they blinded and by who?  It is not that simple is it.

  • Guest1

     Dr Mikovits has only eve been shown to have integrity. Now lets examine Dr Coffin’s research and why Science is not investigating that.

  • Guest1

     Are you a fatigue patient? 

  • Guest1

     Wrong read the details. 

  • Guest1

     Tony patient you have been told before.
    Patient 1199 is not in table 4, but they are in table 1 and table 2.

    You are making things up, read the papers properly.

  • Guest1

     Yes it will be.  Looks like we can pass it on without reprimand at this time.

  • Guest1

     Singh never clinically validated her CFS assays. 

    All samples were treated the same in Lombardi et al.  Both controls and patients.  

  • Guest1

     Then how do you know that?  The study is Fauci’s.  Lets not pretend differently.

  • Synapse13

     I think it’s goes too far to accuse them of impropriety, especially considering Dr. Ruscetti’s good reputation.  Did they make a mistake?  Likely.  But did they intentionally try to hoodwink people?  I find that impossible to believe.  Why would someone with a reputation to protect even consider doing something like that?  Personally, that’s just as nutty as the folks who believe in XMRV as a religion.  I don’t think Dr. Lipkin would be hiring Dr. Miscovits if it were the case.

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