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