Posts Tagged ‘XMRV’

XMRV: More nails in the coffin

5 June, 2011

Except that the title could be “More nails from the Coffin”, given the involvement of someone of that name in amassing the growing weight of evidence against XMRV as an actual natural pathogen – but I digress.

The Nature News blog of 31st May has a very damning collation of views and evidence from around the scientific community – but chief among these is the fact that Science, which published the original paper describing the finding of XMRV in human-derived specimens, has called on the authors to retract it.  The evidence – partly gathered by John Coffin – seems clear: XMRV is a recombinant retrovirus which is a chimaera of two mouse viruses which got into cells derived from a human prostate tumour when these were cocultured with mouse cells.  It is not a “natural” virus, but a laboratory accident; it probably has no relevance to any human disease.

Another interesting and more philosophical view derived from the XMRV saga is that of The Independent, of 3rd June: Steve Connor in “Science Studies” points out that this is, in fact, how science really works – or should work.  That is, that someone publishes something that is really interesting – but which becomes contentious because other can’t replicate it, and eventually is wholly or partially discredited.  All out in the open, in the scientific press.

Some folk – acting with perfect hindsight – then bemoan the fact that the original article was published at all; others are horrified at the waste of money as people dig around and around in the same hole.  What they forget is that progress has been made, whether or not the initial revelation was in fact true.  And that is how science should work.

And because of that sort of iteration, XMRV is going the same way as cold fusion, folks.  And here’s a goodbye….

…and again, XMRV. Or absence thereof.

14 May, 2011

So it is, again, we are driven to report evidence-based absence of evidence for a very contentious virus: the murine retrovirus known as XMRV.  From a preprint online publication in Journal of Virology:

Absence of XMRV and other MLV-related viruses in patients with Chronic Fatigue Syndrome
J. Virol., published ahead of print on 4 May 2011 doi: doi:10.1128/JVI.00693-11

Clifford H. Shin, Lucinda Bateman, Robert Schlaberg, Ashley M. Bunker, Christopher J. Leonard, Ronald W. Hughen, Alan R. Light, Kathleen C. Light, and Ila R. Singh

“Chronic fatigue syndrome (CFS) is a multi-system disorder characterized by prolonged and severe fatigue that is not relieved by rest. Attempts to treat CFS have been largely ineffective primarily because the etiology of the disorder is unknown. Recently CFS has been associated with xenotropic murine leukemia virus-related virus (XMRV) as well as other murine leukemia virus (MLV)-related viruses, though not all studies have found these associations. We collected blood samples from 100 CFS patients and 200 self-reported healthy volunteers from the same geographical area. We analyzed these in a blinded manner using molecular, serological and viral replication assays. We also analyzed samples from patients in the original study that reported XMRV in CFS. We did not find XMRV or related MLVs, either as viral sequences or infectious virus, nor did we find antibodies to these viruses in any of the patient samples, including those from the original study. We show that at least some of the discrepancy with previous studies is due to the presence of trace amounts of mouse DNA in the Taq polymerase enzymes used in these previous studies. Our findings do not support an association between CFS and MLV- related viruses including XMRV and off-label use of antiretrovirals for the treatment of CFS does not seem justified at present.”

I would have said “enough said, then!”  Except that this will not be the end.  Oh, no….

InCROIable quatre!

3 March, 2011

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!


* OK, maybe only scientifically

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