TWiV 136: Exit XMRV

5 June 2011

nude mouseHosts: Vincent Racaniello, Alan Dove, Rich Condit, and Stephen Goff

Retrovirologist Stephen Goff joins Vincent, Rich, and Alan for a discussion of recent papers on the retrovirus XMRV and its association with chronic fatigue syndrome and prostate cancer.

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Links for this episode:

Weekly Science Picks

Alan – The Demon-Haunted World by Carl Sagan
Rich
– Trends in annual rates of death (pdf)
Stephen – Unexpected inheritance (PLoS Pathogens)
Vincent – Beyond the human eye

Listener Pick of the Week

Raihan  – Bruce Aylward: How we’ll stop polio for good (YouTube)

Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

  • setal

    Thanks for all the coverage of this.

    I wonder how the XMRV saga will end up affecting CFS research in the long-run, and whether it will have drawn attention and a new sense of moral impetus to the problem, or will have just strengthened the association between CFS and quackery, putting off better researchers from getting involved?

  • Mary

    hmm… there was 18 comments earlier, they seem to have disappeared..ooops!

  • Guest

     XMRV IS NOT OVER!

    Restricted infection of xenotropic murine leukemia virus-related virus in human lymphoid tissue

    http://www.retrovirology.com/c

    Absence of xenotropic murine leukaemia virus-related virus in Danish patients with multiple sclerosis

    http://www.retrovirology.com/c

    Heme oxygenase-1 activation inhibits XMRV pathogenesis and carcinogenesis in prostate cancer cells

    http://www.retrovirology.com/c

    XMRV replicates preferentially in mucosal sites in vivo: Relevance to XMRV transmission?

    http://www.retrovirology.com/c

    A prototype RT-PCR assay for detection of XMRV in multiple human sample types

    http://www.retrovirology.com/c

    Immune correlates of XMRV infection (Lombardi, Mikovits, etc)

    http://www.retrovirology.com/c

    Prevalence of XMRV in blood donors, HTLV and HIV cohorts

    http://www.retrovirology.com/c

    The effects of XMRV gene expression on the mouse prostate

    http://www.retrovirology.com/c

    XMRV: usage of receptors and potential co-receptors

    http://www.retrovirology.com/c

    Cell line tropism and replication of XMRV

    http://www.retrovirology.com/c

    Structure of the xenotropic murine leukaemia virus-related virus matrix protein

    http://www.retrovirology.com/c

    Development of XMRV producing B Cell lines from lymphomas from patients
    with Chronic Fatigue Syndrome (Ruscetti, Mikovits and others)

    http://www.retrovirology.com/c

    Multi-laboratory evaluations of XMRV nucleic acid (BWG report)

    http://www.retrovirology.com/c

    Serologic and PCR testing of persons with chronic fatigue syndrome in
    the United States shows no association with xenotropic or polytropic
    murine leukemia virus-related virus

    http://www.retrovirology.com/c

    XMRV infection in human diseases

    Otto Erlwein , Mark J Robinson, Steve Kaye, Myra O McClure, Marjorie M
    Walker, Anup Patel, Wun-Jae Kim, Mongkol Uiprasertkul, Ganesh
    Gopalakrishnan, Takahiro Kimura and Kikkeri Naresh

    http://www.retrovirology.com/c

    Murine leukemia viruses (MuLV) and Xenotropic MuLV-related viruses exhibit inter-tropic complex recombination patterns

    Mattia CF Prosperi , William M Switzer, Walid Heneine and Marco Salemi

    http://www.retrovirology.com/c

    Detection of MLV-like gag sequences in blood samples from a New York state CFS cohort

    Maureen R Hanson , Li L Lee, Lin Lin, David E Bell, David Ruppert and David S Bell

    http://www.retrovirology.com/c

    Human infection or lab artifact: will the real XMRV please stand up?

    Robert H Silverman

    http://www.retrovirology.com/c

  • RRM

    This podcast is not only available through virology.ws, but also through TWiV.tv. I am sure that is where the comments are. : )

  • Guest

    interesting to hear dr Goth about xmrv, he really is a good scientist!

    it would be really great if you could hear from one of the pro xmrv group. Perhaps you could have them on your show?

    Dr Frank Ruscetti – is pro XMRV http://ccr.cancer.gov/staff/staff.asp?profileid=5488

    Dr Sandra Ruscetti – is pro XMRV http://ccr.cancer.gov/staff/staff.asp?profileid=5518

    Robert Silverman – is pro XMRV http://www.lerner.ccf.org/cancerbio/silverman/

    I think its very important you have one of these scientists on your show, so we can hear what work they are doing and what there thoughts are.

  • Itsnotautism

    Speaking way too soon on this subject Dr. R.  Its not over, even your colleague Dr. Lipkin has not written off XMRV.

  • Mary

    thanks rrm…  that’s where I saw them…..

    this was a great show!

  • Jason Douglas

    There are prominent scientists that do not believe HIV causes AIDS, should they be included in HIV/AIDS discussions?

  • Jason Douglas

    Yes it is. And your links are busted.

  • Anonymous

    @490ed922a3d3eb61283a9882442e7cea:disqus  Journalist Ewen Callaway did an excellent “second day” piece on just this question. Despite the usual incessant whining by poor put upon Dr. Wessely, comments from CFS expert Dr. Komaroff, Dr. Mangan of the NIH  and virologist Dr. Paul Kellam were all thoughtful and forward looking. http://www.nature.com/news/2011/110603/full/news.2011.347.html?s=news_rss&utm_source=feedburner&utm_medium=twitter&utm_campaign=Feed%3A+news%2Frss%2Fmost_recent+(NatureNews+-+Most+recent+articles)

  • Anonymous

    It was a very strange show, with lots of posturing.

  • Anonymous

    Mangan is towing the line and saying XMRV is over.  But now we have lots of studies finding the virus.

  • Jugglingchessman

    I am concerned that the listener pick may be malware infected(I note that the URL is “youtu.be” not youtube.com)

  • Anonymous

    Prevalence of XMRV in blood donors, HTLV and

    HIV cohorts

    http://www.retrovirology.com/content/pdf/1742-4690-8-s1-a222.pdf

    XMRV is a human retrovirus!

    Conclusions
    XMRV seroprevalence ranged from 0 – 0.6% in US blood
    donors, HIV-1 infected and HTLV uninfected subjects.
    Notably, 4.1% of Japanese HTLV-I infected individuals
    were p15E reactive. Inspection of sequence homology
    between HTLV and XMRV revealed a high level of conservation
    within the immunodominant region of HTLV
    gp21 suggesting increased seroreactivity is due to crossreactive
    antibodies.

  • Anonymous

    I’m afraid it has now been reported that this strain of nude mice, NU/NU and Hsd were not used in the preperation of the 22Rv1 cell line.The authors of the paper have been contacted by the editors of Science and have been asked to deny this fact. We will await their response with interest!  I believe that this matter is to be discussed in the conference in Belgium.  

    The most likely explanation is that these sequences were actually transferred from humans to the mice.  Which should have been proposed in the paper. This has been reinforced by the fact that this mouse strain has been kept isolated from wild mice since its creation. Knox et al. used the PCR assay which had only detected gag sequences in 7% of patients in the Lombardi study when testing Dan Petersons patients and reduced the DNA concentration while doing so and for good measure increased the annealing temperatures.  The likelyhood figures are just plucked out of thin air.  

    Xenotropic Polytropic hybrid MLVs are routinely generated in infected mice.  The use of PCR assays, which have high analytical sensitivity but unknown clinical sensitivity, should be discouraged as negative findings do not prove the absence of target viral sequences.  20 months have been lost because of this fiasco.

  • Anonymous

    Not one study has attempted to replicate Lombardi et al.

  • Anonymous

     @Gob987:disqus   So are you arguing that biomarkers, accurate diagnostics and treatments that move beyond the psychological are not needed? Or maybe even that more funding than the NIH also currently devotes to hay fever is not needed either?  Because Dr. Mangan apparently thinks so. 

  • anon

    This was a great podcast, and I’ve been hoping each week since the papers came out that you would cover it.  Dr. Goff really helped explain what the papers were saying.  As always, I love twiv!

  • Anonymous

    Which post are you responding to?

  • Guest
  • Guest
  • Justin Reilly, esq.

    Why exactly is it that every fake anti-science “CFS” study is just peachy, but one of the best bona fide ME studies of all time is asked to be retracted?? Based on the fact that some inferior studies haven’t been able to confirm it, while others, published and unpublished have? This is obviously just one more transparent attempt to crush ME patients and science. 

  • Justin Reilly

    Mangan said at the SoK workshop that there will be no increase in funding of ME at NIH.  The NIH invitation for grant proposals said any other definition than Fukuda (including CCC) had to have a good argument behind it, etc.  NIH doesn’t care if we live or die, as usual.

  • Justin Reilly

    So the links are busted.  It doesn’t mean these and other evidence of HGRVs being human infections do not exist.

    We do not know for sure whether or not HGRVs are associated with ME.  They may well be unassociated, but we DO NOT KNOW yet.  So ‘they’ should stop saying that we know for sure that the two are unassociated. And they should stop accusing those who point this out of being unscientific.  There is a very long and very clear history of NIH, CDC, the UK government and a small cadre of UK psychiatrists waging a war on ME science and patients.  The present shenanigans are more biased attempts to crush valid ME science.

  • setal

    Hmmm… apparently Wessely thinks that he ‘is reviled by many with CFS for emphasizing the neuropsychiatric aspects of the syndrome’.  He always comes up with some explanation for it the avoids addressing his own mistake of the harm they’ve done to patients.  He probably sees this as a healthy neuro-cognitive response.

    Thanks for the link.  CFS is such a difficult condition to do meaningful research on that I can understand the temptation not to bother with it.  The exciting thing about XMRV was that it gave science a really solid starting point – without that, it’s difficult to know how to best move forward.

  • Anonymous

    @b43054973034ee54cce92da7d3459780:disqus  So, same question. Are disagreeing with Dr. Mangan that biomarkers, accurate diagnostics and treatments are necessary? I don’t think you read the article very closely. 
    Dr. Mangan acknowledges the current funding limitations, but adds that there is money elsewhere for relevant issues such as exercise, pain etc.  Dr. Glaser for instances went through the cancer SEP. In case you haven’t read a headline in the past few years – the political parties are locked in a political battle that benefits no one.  Yes, funding needs to be increased, but if you know a magically way to make it instantly appear my checking account could use a few bucks as well. :DYou also said the NIH doesn’t care if we live or die as usual. Dr. Mangan says, “It’s an illness that’s not going away and the NIH is not
    going to turn its back on it.”  Since Dr. Mangan actually works for the NIH I’m going to assume he knows what he is talking about. 

  • Anonymous

    @Gob987:disqus Your toeing (towing) the line comment. 

  • Pingback: XMRV: Human Retrovirus Mistake | The Health Matters Show With Cinda Crawford()

  • Anonymous

    Mangan is towing the line.  You seem to be plucking comments from thin air.  Here is my comment again.

    “Mangan is towing the line and saying XMRV is over.  But now we have lots of studies finding the virus.”

  • Guest
  • Justin Reilly

    Alan Dove is needlessly insulting.  Do you really want him to be an ‘ambassador’ of science on your show?  I guarantee having him on your show will put many people off to science.
    http://alandove.com/content/2011/06/our-cross-to-bear/

  • Karin

    Prof. Racaniello,

    Thank you for another interesting TWiV on XMRV. I heard you discuss the findings that XMRV added to human blood was quickly destroyed, likely by serum complement, making it very unlikely that XMRV was able to infect humans.

    However, I just see this new article in Virology, that seems to contradict the above findings:

    An XMRV Derived Retroviral Vector as a Tool for Gene Transfer
    Virology Journal 2011, 8:284 
    http://www.virologyj.com/content/8/1/284/abstract

    How could XMRV be successfully used as a gene transfer vector if it is immediately damaged by serum complement? Am I missing something?

    I am very interested in the answer, because the fact that one, XMRV is ubiquitous as a contaminant in biological product, and two, that it is able to infect human cell lines, makes me really wonder if it could be infecting humans and cause disease… I thought the argument that it is immediately inactivated by exposure to serum complement was very reassuring…

  • drosha

    Maybe I can help:

    1. Gene transfer doesn’t necessarily mean gene therapy
    2. Gene therapy doesn’t need to be done through IV injection, it can be done ex vivo (meaning by infecting the cells outside the body and then putting them back, or by injecting the tissues)
    3. And most importantly, what’s damaged by serum is the outside of the virus particle. You don’t need to (and almost always you don’t) use the wild type envelope protein of the retrovirus in gene therapy. Retroviruses can be pseudotyped by other envelope proteins (either from other retroviruses or even other viruses such as VSV).

  • Anonymous

    The authors of Paprotka et al should all be ashamed of themselves from claiming the virus was created in the 90s based on the evidence presented.  A totally unscientific was to go about research.

  • neil

    Hi

    I’d like to thank prof racaniello (and guests) for doing these podcasts.  Ihave me/cfs and the xmrv theory both worried me and filled me with hope.  thanks to your coverage i feel i understand a little of the science and no longer believe that xmrv is a disease causing human gamma-retrovirus.  It’s difficult to know what or who to believe sometimes so i’m grateful to get information from independent commentators. 

    Best regards

    Neil

  • Shane Carlson

    I find Dove’s reader recommendation of “The Demon Haunted World” by Carl Sagan to be dripping with irony.   In the reviews on the page he links to the book is described as 
    “A clear vision of what good science means and why it makes a
    difference. . . . A testimonial to the power of science and a warning of
    the dangers of unrestrained credulity.”

    Given Dove’s previous mischaracterizations about the history of  CFS (and the very nature of CFS itself) and his defensiveness regarding how he indirectly profits from these BELIEFS, I have to agree that his recommendation is appropriate but perhaps in a manner that reveals more about himself than he intended.

  • window

    I don’t really think it’s fair to currently class these people as equivalent to HIV denialists, do you?

    I think it would be great to hear Racaniello talk this through with them.  Apparently Frank Ruscetti was still sounding positive about XMRV at the recent symposium, and it would be interesting to hear why.

    So far, we’ve not heard much debate between the two sides – just people brining out conflicting data.  The ‘negative’ side have got some compelling evidence behind them, but I’d still be interested in hearing the different arguments going on behind this, and how those continuing their XMRV work account it.

  • Tony Mach

    Exit XMRV, enter Enteroviruses?

    From what I have read sofar, I think Enteroviruses are behind ME/CFS.
    First of all, there is the most recent work by Dr. John Chia. He finds VP1 enterovirus protein in about 80% of gut biopsies of people with ME/CFS he tested. Furthermore the viruses he find show about 80% homology to Coxsackie B.
    http://chronicfatigue.stanford.edu/infections/entero-experts.html

    The work of John Chia is based on the earlier work of British scientists, (mainly James Mowbray if I’m not mistaken) who found VP1 in gut and muscle biopsies of ME/CFS patients.But for me the key (and the best clinical description of the earlier outbreaks of ME/CFS I could find) is “The saga of Royal Free disease” by A. Melvin Ramsay: He describes how in villages in Icland in 1948 that suffered an ME/CFS outbreak were sparred from a following Polio outbreak that hit other villages. And he describes how an Polio outbreak in Adelaide ceased abruptly to be replaced by an ME/CFS outbreak.Furthermore, if you haven’t read it, I can recommend the book Osler’s Web to get a feeling why ME/CFS is such a minefield – and a nightmare for those suffering from this disease.

    (I posted it on the Coxsackie post before, sorry)

  • Anonymous

    Goff actually repeated several assumptions as fact and was incorrect on many points.

    Here is one example.  Goff stated that PreXMRV-1 and 2 are xenotorpic.  If that were correct they could never have recombinated to create XMRV, as this virus is a polytropic xenotropic hybrid. 

  • http://www.facebook.com/profile.php?id=1608101635 John Buettner

    Links cab easily be fixed. Here’s one:  http://www.retrovirology.com/content/8/S1/A234
    If that’s too long and gets truncated, try this: http://goo.gl/V6TVj

    Why are so many organizations ready to throw out the baby with the bath water? It almost smells of conspiracy.

  • http://www.virology.ws profvrr

    The link is fine but I changed it to the full URL anyway.