InCROIable quatre!

This morning, I’m afraid I experienced rather more secondary effects from the previous night’s entertainment. Thanks to my friend Sylvie, I got invited to the Walker lab party, where I found myself hopelessly outclassed, both scientifically and alcoholically*. Over the course of the evening, I’m sure we worked out exactly how to both cure HIV infection, and produce an effective vaccine, but by the time I awoke (somewhat disorientedly) this morning, it had all disappeared in a mist of Sam Adams.

XMRV – the incredible vanishing virus

As you may recall, in 2009 a new retrovirus called XMRV was reported to be associated with chronic fatigue syndrome (CFS – Lombardi and colleagues 2009). It had previously been reported to be associated with prostate cancer. These results have been the subject of much controversy, and today there was a one-hour discussion session on XMRV. Speakers gave two-minute presentations of their recent results, and this was followed by comments from the floor. The highlights were as follows:

Four different labs, using different techniques reported that they basically did not find XMRV in humans.

William Switzer (CDC, USA) – Tested 45 CFS patients and 42 controls using the same technique as that reported in the Lombardi paper, and looked for serology by Western blot. ZERO POSITIVES.

Timothy Henrich (Brigham and Women’s Hospital, USA) – Tested 293 diverse and varied patients, and 3 CFS patients reported to be XMRV positive in a previous study by nested PCR. ZERO POSITIVES.

Mary Kearney (NCI Frederick, USA) – developed a quantitative PCR assay with single-copy sensitivity to detect XMRV. Reported experimental infection in two macaques. In those two animals, XMRV proviral DNA persisted in blood cells, and was consistently detected. Using this technique, they tested 134 prostate cancer patients, and 4 patients previously reported as XMRV positive in the Lombardi study. ZERO POSITIVES.

Finally, Oya Cingoz (Tufts, USA) and Vinay Pathak (NCI Frederick, USA) reported on the origins of XMRV. This virus was first described in a protstate cancer cell line called 22Rv1, which secretes XMRV. This cell line definitely carries the virus, but how did it get there?

Like many immortalized cell lines, 22Rv1 started out as a human tumor transplanted into immunodeficient “nude” mice in what is known as a xenograft. It was passaged in this way many times in different types of mouse – suggesting that 22Rv1 may have acquired XMRV from its mouse hosts. This is plausible because mice carry many types of endogenous retroviruses in their genomes. Cingoz and Pathak showed that althoug XMRV is not identical to any known mouse retroviruses, the left-hand (5′) half of XMRV is identical to one particular mouse retrovirus, while the right-hand (3′) half is identical to a different mouse retrovirus. XMRV is therefore a new virus produced by recombination between two distinct mouse viruses. This all happened since 1992, when the prostate cancer that gave rise to 22Rv1 was first transplanted into nude mice. It is not a virus that has been circulating in human beings.

One would have liked to have heard the other side of the story from the authors of the Lombardi paper, but they didn’t show up to face the data. I guess that tells its own story.

So just to wind up, XMRV is NOT associated with CFS, and does not appear to be present in the human population (although one might wonder whether researchers working with the 22Rv1 line might in fact be at risk of infection).

If you have CFS, do not buy a test for XMRV (they are entirely BOGUS, as Simon Singh might have said), and do not ask your doctor for antiretroviral medication (unless you are HIV positive, of course). It will be a waste of money, and you will just get the side effects of the medication, without any benefit.

And that was it for the 18th CROI!

Dorian

* OK, maybe only scientifically

…and my thanks, Dorian, for a job really well done! – Ed

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22 Responses to “InCROIable quatre!”

  1. glenp Says:

    What do you propose for the patients?

    What about Alters abstract?

    Its about time that XMRV, MLV’s and related are studied further. Go and learn from the ones that know how to find them. Sadly this conference leads to the backslide of reserch. ITS TOO BAD BUROCRISY HAS SUCH A KEY ROLE
    Pleeez

    • Ed Rybicki Says:

      Glenp: think before you type…as it is, who knows what Alter’s abstract says?? And what role did bureaucracy – note sp – play here? I’d say debunking taurine excreta was more important?

      Ed

  2. Andrea Says:

    Just to clarify, Dr. Judy Mikovits and Drs. Ruscetti were not invited. You might want to question why the researchers who previously found XMRV (both published and unpublished) and related MRVs (Alter and Lo) were not present at the conference. The ‘asymmetry’ was very telling.

    • Alan Says:

      Just to clarify further, one does not have to be “invited” to CROI. Any researcher in the field can simply register and attend. Why some chose not to do so is a question only they can answer.

      • Ed Rybicki Says:

        Hear hear! Not that I am involved in any way, but no-one has ever negatively vetted my application to go to any scientific meeting in the last 29 years.

  3. chris Says:

    Ed, glen is sick with a neurological disease and trying his best. Please cut him some slack. We just want answers.

  4. DMcILROY Says:

    Glenp: All the groups whose work I summarized in the post have expertise in working with these types of virus, and they are all able to find XMRV when it is actually there. In particular, the results presented by Mary Kearney show that there is no problem in detecting XMRV in a blood sample after an experimental infection.

    I have no positive recommendation to give for CFS patients (and indeed, I am not an MD), but it is clear that treating a non-existent XMRV infection with anti-retroviral drugs is not going to help.

    DMc

  5. shameful Says:

    If you were a Government, what would be cheaper for you?

    A) To spend billions of dollars/euros in research, disability pensions, lawsuits, compensations, medical treatments, social aid, etc, etc, etc.

    B) To spend a little in arranging all this stuff to remain covered and dismissed as psychiatric. Getting negative stdies is cheap and easy. Problem solved.

    • Ed Rybicki Says:

      This is just so paranoid as to take one’s breath away: right up there with the extra Kennedy gunman and black helicopters.

      Get a grip!! Or don’t bother commenting on what is – or should be – a serious evidence-based discussion.

  6. Vickie Taylor Says:

    Ed,

    If I were as ignorant of the history of research on the correlation of XMRV with prostate cancer and ME/CFS as you are, I would be ashamed to write a blog revealing my ignorance.

    It is obvious that you have not read the Lombardi paper published by Science, the Lo and Alter paper, the research with Macaque monkeys by Ila Singh, the Hanson, MR, et al, paper, the Japanese paper that found about 3% of healthy people were infected with XMRV, the German paper that found XMRV in a group of patients with lung disease (Fisher N, et al, and the published rebuttals explaining why so many groups are having trouble finding XMRV in CFS and prostate cancer patients.

    Perhaps there is a bit of bias at work here.

    Vickie Taylor
    ME/CFS 36 years

    • Ed Rybicki Says:

      Vickie:

      If you had actually read the series of articles that Dorian McIlroy wrote, and especially the first one, you will have seen that they are guest blogs.

      That is, they are not written by me. So that barb flew astray rather, didn’t it? Dorian, does the tag fit you, or are you not in fact so ignorant?

      Second, I have actually read a number of papers and commentaries on XMRV, and as a reasonably well-informed professional virologist, I have to say that the evidence is not overwhelmingly in favour of it being causatively involved in any human disease. Are you a virologist, Vickie? If you are not, I could tell you that I can find you “evidence” for the complete fabrication of all evidence for the existence of Hepatitis C virus; evidence that HIV does not exist, or if it does, does not cause disease; that ME is caused by parvoviruses, and so on. Of course, I could also find you a lot of better evidence, possibly less accessible to the layperson, that proves the opposite.

      So no, Vickie, there is no bias involved here – simple assessment of the evidence on offer.

  7. jim Says:

    Well the WPI and other ones to find positives were strickly forbidden to join this years CROI. SO you have to let them in if you want to hear the opinion.

  8. Mary Says:

    “One would have liked to have heard the other side of the story from the authors of the Lombardi paper, but they didn’t show up to face the data. I guess that tells its own story.”

    It’s been stated in another comment, but it can’t be stressed enough, that the authors of the Lombardi paper were not invited to the conference. This, indeed, “tells its own story,” and it’s an alarming one.

    • Ed Rybicki Says:

      “…the authors of the Lombardi paper were not invited to the conference…”

      Why did they simply not apply to come, like 99% of the other delegates? Really, really…!

  9. Jennifer Henry Says:

    The controversial topic of XMRV will be dicussed at a symposium at the New York Academy of Sciences on March 29, 2011 on ‘Pathogens in the BLood Supply’. Judy Mikovots will be one of the speakers, and I invite you to peruse the program and join us in the audience if you wish to debate these issues in person.

    More details at http://www.nyas.org/BloodSupply

  10. Monday Extras! « The Abbot Lab Says:

    [...] an interesting summary of current XMRV research from the recent Conference on Retroviruses and Opportunistic Infections over at ViroBlogy. [...]

  11. DMcILROY Says:

    Sorry that I’m a bit late getting back to the comments, but there are several points that need to be answered.

    Firstly, were the authors of the Lombardi paper excluded from the conference?

    Generally, to present results at a scientific conference, you submit a resumé of the work you are going to talk about, then the organizing committee chooses which of the submitted abstracts are presented, either as posters or orally. The CROI works like this, and as Ed pointed out, anyone can apply to attend the conference (although preference is given to applicants who have an accepted abstract).

    So I guess, the question is, did the organizing committee exclude an abstract from the Mikovits group? I will contact John Coffin (who was president of the organizing committe, and has a particular interest in the XMRV story) and try to get an answer from him. I will come back here with his comments.

    Secondly, are all the negative studies (that is, the majority of the work carried out on this virus) part of a big cover-up?

    As far as I know, none of the scientists who found negative results have any particular axe to grind with respect to CFS/ME, and as far as I can tell, they all started their work with an open mind on the question. Nobody went out to find a negative result on purpose. The objective was to test whether the association reported initially by Lombardi and colleagues was reproducible. If it had been then Lombardi et al. would have made an important discovery, that could have led to effective treatment and prevention of CFS/ME. However, when the vast majority of results come out negative, then you just have to accept that the CFS/XMRV connection just does not stand up to scutiny, then go on looking for another cause for the disease.

    This is not a conspiracy, it is just the way science works. Sticking to an idea (ie. that CFS is related to XMRV infection) that has been rigorously tested, and found to be incorrect does not help anybody.

    Finally, with respect to ignorance of previous work, there are two points worth making.

    Firstly, this is not the first time that a virus infection has been postulated as the cause of CFS/ME. Many different viruses have been proposed as causative agents over the last 20 years or so. In all cases, the initial findings were not replicated, and no real causal link was found. This track record alone is a good reason to be very cautious whenever anyone claims to have found that a virus is responsible for CFS/ME.

    Secondly, other retroviruses, closely related to XMRV, have previously been linked to human disease, only for those studies to turn out (after a lot of independent testing by other labs) to have been due to false positives. A good explanation of why this happens is given by Robin Weiss in this open access article:

    http://www.biomedcentral.com/1741-7007/8/124

    Once again, the track record should teach us to be cautious when anyone claims that a strange mouse retrovirus is related to a human disease. That is not to say that such an idea is patently ridiculous or impossible – just that such claims need to be validated carefully by independent groups before they are accepted as correct.

    DMc

    • Ed Rybicki Says:

      Thank you Dorian! As I said: this is HOPEFULLY an evidence-based discussion; conspiracy theorists and ad hominem attackers need not reply further.

      Ed

  12. DMcILROY Says:

    John Coffin kindly answered my mail, and had this to say about selection of speakers for the XMRV session.

    “No researcher who registered for CROI before the deadline was
    forbidden to attend. Of the more than 4000 participants at CROI,
    less than 100 were invited to speak, and none of the speakers on XMRV
    was invited. All the XMRV talks were selected from submitted
    abstracts.
    Submitted abstracts are confidential, as is their review, so I cannot
    discuss any specifics of the process, except to note that only about
    half of them were accepted for presentation this year.”

  13. TWiV 129: We’ve got mail Says:

    [...] Discussion about CROI at ViroBlogy [...]

  14. Ed Rybicki Says:

    I have cancelled a couple of posts to this discussion because of the ad hominem attacks in them – and because, in one case, the email address of the person posting did not exist.

    I repeat, this is a forum for evidence-based discussion of virology-related topics – and in this case, the virology and epidemiology of XMRV.

    It is NOT a forum for parading conspiracy theories and making personal attacks on people who are reputable professionals.

    SO don’t bother to post such things, because I will delete them out of hand.

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