XMRV - Innocent on All Counts?

A bombshell has just gone off in the continuing debate over XMRV, the virus that may or may not cause chronic fatigue syndrome. Actually, 4 bombshells.

A set of papers out today in Retrovirology (1,2,3,4) claim that many previous studies claiming to have found the virus haven't actually been detecting XMRV at all.

Here's the rub. XMRV is a retrovirus, a class of bugs that includes HIV. Retroviruses are composed of RNA, but they can insert themselves into the genetic material of host cells as DNA. This is how they reproduce: once their DNA is part of the host cell's chromosomes, that cell is ends up making more copies of the virus.

But there are lots of retroviruses out there, and there used to be yet others that are now extinct. So bits of retroviral DNA are scattered throughout the genome of animals. These are called endogenonous retro-viruses (ERVs).

XMRV is extremely similar to certain ERVs found in the DNA of mice. And mice are the most popular laboratory mammals in the world. So you can see the potential problem: laboratories all over the world are full of mice, but mouse DNA might show up as "XMRV" DNA on PCR tests.

Wary virologists take precautions against this by checking specifically for mouse DNA. But most mouse-contamination tests are targeted at mouse mitochondrial DNA (mtDNA). In theory, a test for mouse mtDNA is all you need, because mtDNA is found in all mouse cells. In theory.

Now the four papers (or are they the Four Horsemen?) argue, in a nutshell, that mouse DNA shows up as "XMRV" on most of the popular tests that have been used in the past, that mouse contamination is very common - even some of the test kits are affected! - and that tests for mouse mtDNA are not good enough to detect the problem.

• Hue et al say that "Taqman PCR primers previously described as XMRV-specific can amplify common murine ERV sequences from mouse suggesting that mouse DNA can contaminate patient samples and confound specific XMRV detection." They go on to show that some human samples previously reported as infected with XMRV, are actually infected with a hybrid of XMRV and a mouse ERV which we know can't infect humans.
• Sato et al report that PCR testing kits from Invitrogen, a leading biotech company, are contaminated with mouse genes including an ERV almost identical to XMRV, and that this shows up as a false positive using commonly used PCR primers "specific to XMRV".
• Oakes et al say that in 112 CFS patients and 36 healthy control, they detected "XMRV" in some samples but all of these samples were likely contaminated with mouse DNA because "all samples that tested positive for XMRV and/or MLV DNA were also positive for the highly abundant IAP long terminal repeat [found only in mice] and most were positive for murine mitochondrial cytochrome oxidase sequences [found only in mice]"
• Robinson et al agree with Oakes et al: they found "XMRV" in some human samples, in this case prostate cancer cells, but they then found that all of the "infected" samples were contaminated with mouse DNA. They recommend that in future, samples should be tested for mouse genes such as the IAP long terminal repeat or cytochrome oxidase, and that researchers should not rely on tests for mouse mtDNA.

They're all open-access so everyone can take a peek. For another overview see this summary published alongside them in Retrovirology.

I lack the technical knowledge to evaluate these claims, no doubt plenty of people will be rushing to do that before long. (Update: The excellent virologyblog has a more technical discussion of these studies.) But there are a couple of things to bear in mind.

Firstly, these papers cast doubt on tests using PCR to detect XMRV DNA. However, they don't have anything to say about studies which have looked for antibodies against XMRV in human blood, at least not directly. There haven't been many of these, but the paper which started the whole story, Lombardi et al (2009), did look for, and found, anti-XMRV immunity, and also used various other methods to support the idea that XMRV is present in humans. So this isn't an "instant knock-out" of the XMRV theory, although it's certainly a serious blow.

Secondly, if the 'mouse theory' is true, it has serious implications for the idea that XMRV causes chronic fatigue syndrome and also for the older idea that it's linked to prostate cancer. But it still leaves a mystery: why were the samples from CFS or prostate cancer patients more likely to be contaminated with mouse DNA than the samples from healthy controls?

Robert A Smith (2010). Contamination of clinical specimens with MLV-encoding nucleic acids: implications for XMRV and other candidate human retroviruses Retrovirology : 10.1186/1742-4690-7-112

A PCR Primer

The latest episode in the nail-biting scientific drama of "Does The XMRV Virus Cause Chronic Fatigue Syndrome?" has arrived, in the form of a paper in PNAS. A team of virologists led by the renowned Harvey Alter reported finding various XMRV-like viruses, but not XMRV itself, in chronic fatigue patients.

There's been plenty of excellent coverage of this new study, but most of it has come from specialists and has assumed a certain degree of technical knowledge. So here's my attempt to provide a summary for the non-expert, writing as someone who last got his hands dirty in a molecular lab 5 years ago...

The key to the controversy is PCR, a very useful technique invented by a guy on acid (kind of). PCR means Polymerase Chain Reaction. Polymerase is an enzyme which copies DNA. If you ask it nicely, it also copies the copies, then copies the copies of the copies, and so on. Thanks to this chain reaction, you can start with a tiny bit of DNA and end up with loads.

Using PCR, you can detect certain DNA sequences, for example, the DNA sequence of XMRV. (XMRV itself has RNA, rather than DNA, but as a retrovirus, it's able to insert itself into the DNA of infected cells.)

Here's how. DNA is a chain, or strand, of simple molecules called nucleotide bases. There are four: A, C, T, and G. Most of the time, DNA molecules are double-stranded, containing two chains of bases paired up (bound) together. Whenever one strand has A, the other has C, and vice versa. T and G pair up in the same way. They can only pair up in that particular way. T can't pair with C, or G, or with another T.
PCR takes double-stranded DNA and makes more of it. It does this by taking each strand and adding a second strand which is the "opposite" (complementary) sequence of the original, with T and A swapped, and C and G swapped.

That's nothing more than a replica of the original double-stranded DNA.

However, there's a catch. Polymerase can't start a strand of DNA out of nothing, it can only make an existing strand longer. So it needs a primer which can bind to the original DNA and provide "something to work with".

No primer, no duplication. The primer has to be specific: it has to be able to pair up with the DNA. This fact allows us to use PCR to detect specific DNA sequences. Suppose you want to know whether a sample of DNA contains a certain gene, and you know that this gene starts with AAAAA, and ends with CCCCC.

You would make some corresponding primers: a forward primer AAAAA and a reverse primer GGGGG. If the gene is present, these primers will bind to the corresponding target sequences bookending the gene of interest. The PCR will work, and you'll end with loads of copies of that gene. Hooray. If not, nothing much happens. Note that the forward primer is the "opposite" of what you might expect, because it has to bind to the complementary strand. The two primers bookend the region to be amplified - see this pic for an explanation of why.

Once you've run the PCR it's relatively easy to tell whether it amplified the gene or not. But remember that PCR doesn't detect genes, it detects primer targets. The DNA in between the target regions could be anything, as long as the primers fit. In fact, you can tell the length of the amplified DNA, which does provide some information. You can also resequence the amplified DNA to see exactly what it is, but that's expensive.

On the other hand, the match has to be exact. If you're testing for a gene starting with AAAAA, and that gene is present except that it starts with AAAAC instead, you won't find it: a single base difference in the primer sequence throws the whole thing off.

So if someone "used PCR to detect dog DNA", what they mean is that they used primers which they think are specific to dog DNA. This relies on two things being true: that the primers do in fact match the DNA of all dogs (not just some breeds of dog) and that they only match dog DNA (not cats, or mice.)

There are also technical considerations. PCR is vulnerable to contamination by unwanted DNA, because it's so sensitive: even a tiny bit of contamination will cause a false positive. Rogue DNA could come from anywhere: from the researcher running the experiment, from other samples in the lab... So, every PCR experiment needs a negative control, a sample known not to contain the gene of interest. A drop of water is the simplest example. If you "detect" the gene in the negative control, you have to try again (after cleaning all your equipment and washing your hands.)

PCR also doesn't always work. It's like cooking: you have to have the right mix of ingredients, the right temperature, the right timing. If not, you'll end up with a mess. This is why every PCR experiment needs a positive control, i.e. a sample in which you know the gene of interest is present. If you fail to detect the gene in the positive control, you have to check the recipe and try again.

How does this relate to the XMRV story? That's another post...

XMRV and Chronic Fatigue Syndrome, Continued (Again)

Yet more twists have emerged in the already serpentine tale of XMRV, the virus that may or may not be responsible for causing some cases of chronic fatigue syndrome (CFS), aka myalgic encephalomyelitis, (ME).

First off, on Saturday 2nd July, a news item in Science magazine reported that two papers on XMRV were about to be published, but that the publication of both was "on hold" because they contradicted each other. One paper, from the US federal Centers for Disease Control (CDC), supposedly found no evidence of XMRV infection while the other one, from the National Institutes of Health and Food and Drug Administration (NIH/FDA), did.

The papers were only rumored to exist at that stage, and the story behind the NIH/FDA paper was particularly complicated. A Dutch magazine called ORTHO reported (see also) that NIH virologist Harvey Alter had given a presentation in Zagreb, Croatia, in which he reportedly said that the original Lombardi et al 2009 results, which first implicated XMRV in CFS

are extremely strong and likely true, despite the controversy...We (FDA & NIH) have independently confirmed the Lombardi group findings.

This was in reference to the still unpublished NIH/FDA paper, which according to Science, has been accepted for publication but currently put "on hold" by the journal PNAS.

However, the Science news was obsolete as soon as it appeared, because the other "on hold" paper, the negative one from the CDC, turned out not to be on hold for very long, if at all. It's now available online at the journal Retrovirology: Switzer et al's Absence of evidence of Xenotropic Murine Leukemia Virus-related virus infection in persons with Chronic Fatigue Syndrome and healthy controls in the United States. It's listed as being published on the 1st July.

The CDC paper Switzer et al, as the rumors predicted, is negative. The authors tested blood plasma from 51 CFS cases and 53 healthy controls and found no evidence of anti-XMRV antibodies; they sent the same samples to a German lab and they confirmed the results. They then tested DNA extracted from blood samples in the same CFS patients and 97 controls, finding no evidence of XMRV DNA using a number of analytical methods; again, a second lab confirmed this. The paper is open access, so you can read it for more details (there are lots).

This is a big deal, because this is the first paper to attempt to replicate Lombardi et al's results in American patients. Several studies have appeared in the months following the original paper, and none of them found XMRV infection in any of their patients or controls. This is mysterious because Lombardi et al found XMRV in 67% of patients, but also in 4% of controls. However, these studies all used European people, raising the possibility that XMRV is just not found in Europe, for whatever reason.


So what exactly is going on here? Maybe only Lombardi et al used the appropriate methods which were able to detect XMRV, and everyone else has been failing to pick it up. However, in my opinion, while this was a reasonable suspicion months ago, it's very unlikely now because (by my count) 6 labs have not found XMRV in CFS patients, using lots of different approaches.

In most cases these labs showed that they were able to detect small quantities of XMRV added into a sample, as a positive control. Switzer et al, for example, say that they were able to detect 10 copies of the virus (not many) mixed into a sample of human DNA; one of the labs they used for a confirmation analysis could detect 4 copies.

There's another possibility - maybe only Lombardi et al were studying the right people. Lombardi et al used a carefully selected subgroup of CFS patients with various neurological and immunological abnormalities suggestive of a "medical" as opposed to a "psychological" disorder. However, the most popular 1994 criteria for CFS are a lot broader than this. Supporters of the XMRV-CFS link say that XMRV is probably associated only with some cases of CFS, and the various failed attempts to confirm XMRV have been looking in the wrong people.

Bearing this in mind, it's notable that the latest Switzer et al paper didn't recruit patients by approaching those who considered themselves to have CFS. Rather they identified cases through population screening: calling random numbers from the telephone directory of Wichita, Kansas, and of sites in Georgia, and asking people whether they were suffering from CFS-like symptoms such as fatigue. People who answered "yes" to enough questions were invited for a medical exam and interview and were diagnosed with CFS if they met the 1994 criteria (though in the abstract these are described as the revised 1994 criteria), as long as their symptoms weren't explained by a known, current medical or psychiatric disorder.

It's fair to say that this will have recruited a very different cross-section of patients than Lombardi et al did. However, in my opinion, while this is important, it doesn't resolve the fundamental mystery of why no-one had XMRV, not even the healthy controls, given that Lombardi et al found XMRV in 4% of healthy people. To my knowledge, this question remains unexplained. Maybe the "on hold" NIH/FDA paper will shed some light...

Finally, those interested in this topic may find my running summary of (I hope) all human XMRV research useful.

Link: virologyblog is also on the case...


Switzer, W., Jia, H., Hohn, O., Zheng, H., Tang, S., Shankar, A., Bannert, N., Simmons, G., Hendry, R., Falkenberg, V., Reeves, W., & Heneine, W. (2010). Absence of evidence of Xenotropic Murine Leukemia Virus-related virus infection in persons with Chronic Fatigue Syndrome and healthy controls in the United States Retrovirology, 7 (1) DOI: 10.1186/1742-4690-7-57

Enserink, M. (2010). Conflicting Papers on Hold as XMRV Frenzy Reaches New Heights Science, 329 (5987), 18-19 DOI: 10.1126/science.329.5987.18

The Case of the Missing Retrovirus

In October 2009, a team led by Vincent C. Lombardi of the Whittemore Peterson Institute reported the presence of a recently discovered virus, XMRV, in 67% of the blood samples from 101 American patients with chronic fatigue syndrome (CFS). XMRV had previously been linked to some cases of prostate cancer.

This sparked intense interest amongst many people and much discussion. But in January this year, Erlwein et al reported that they did not find any evidence of XMRV in the blood of 186 British CFS patients (my post).

Now, a second British study has appeared, and the results are also negative. The paper is Groom et al's Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome. They found no XMRV in 170 British CFS patients or 395 healthy controls. VirologyBlog has an excellent summary of the latest paper.

In order to help people interested in this topic, I've put together a quick summary of all the data on XMRV infection in humans. If I've left anything out or made any mistakes, let me know in the comments. I'll try to keep this list up to date with every new publication - because there are sure to be plenty more.

Overall, the most striking thing about these results is the national differences. XMRV has been detected in 67% of American CFS patients, in 10-25% of American prostate cancer cases, and in 3-4% of healthy Americans. By contrast, in Germany, Britain and Ireland, it's only been detected in 2 Germans, out of a grand total of 1,300 or so European people who have been tested so far using a variety of methods. The situation elsewhere is unclear; one study claimed to detect XMRV in 1.5% of healthy Japanese blood donors but this is unpublished, and the methodology is unclear.

Other than that, it's not clear what's going on here, and it seems to me that it would be premature to conclude anything about XMRV and CFS (or, indeed, cancer) at this stage.

*

Last Updated: 06 July 2010
Please let me know if I have omitted any data (published or unpublished)

Published Papers - CFS

1. Lombardi et al 2009

• Patients: "CDC Fukuda Criteria and the 2003 Canadian Consensus Criteria... presenting with severe disability... their diagnosis of CFS is based upon prolonged disabling fatigue ... cognitive deficits and reproducible immunological abnormalities ... impaired exercise performance with extremely low VO2 max measured on stress testing."
• Origin: USA
• Method A: PCR of DNA from PBMCs
• Result: 68 of 101 patients (67%), 8 of 218 controls (3.7%)
• Method B: PBMC reactivity to anti-MLVp30Gag antibodies
• Result: 19 of 30 patients (63%), 0 of 16 controls (0%)
• Method C: Plasma immunoreactivity to SFFV-Env
• Result: 9 out of 18 patients with XMRV, 0 out of 7 controls

2. Erlwein et al 2010

• Patients: CDC Fukeda criteria "markedly unwell. Few were working, and 19% were members of patient support groups for CFS/ME... The levels of fatigue in this sample were high ... as were levels of disability"
• Origin: London, UK
• Method: PCR of DNA from whole blood
• Result: 0 out of 186 patients (0%)
  

3. Groom et al 2010

• Patients: CDC Fukeda criteria
• Origin: Bristol, Dorset, London, Birmingham, Norfolk and Epsom, UK
• Method A: PCR of gDNA from PBMCs
• Result: 0 of 48 patients (0%)
• Method B: PCR of gDNA, cDNA, or both from PBMCs
• Result: 0 out of 142 patients (0%), and 157 controls (0%)
• Method C: Serum immunoreactivity to XMRV
• Result: 1 out of 160 patients; 25 out of 395 controls; but positives were not considered specific to XMRV, as they also reacted to and neutralized other viruses.

4. Switzer et al 2010 "CDC study"

• Patients: Recruited by random population telephone screening and symptom quizzing (unlike other studies). CDC Fukeda 1994 criteria (but also referred to in the abstract as the "revised" 1994 CDC criteria) and symptoms not better accounted for by medical illness or "current psychiatric disorders considered exclusionary for CFS, which included current melancholic depression, current or lifetime bipolar disorder or psychosis, substance abuse within 2 years and eating disorders within 5 years".
• Origin: Wichita, Kansas, USA and Georgia, USA.
• Method A: Western blotting serology for anti-XMRV antibodies in plasma
• Result: 0 of 51 patients (0%) and 0 of 53 controls (0%)
• Method B: ELISA serology for anti-XMRV gag and pol antibodies in plasma, performed by RKI.
• Result: 0 of 51 patients (0%) and 0 of 53 controls (0%)
• Method C: PCR of DNA from PBMCs or whole blood for XMRV gag and pol
  
• Result: 0 of 50 patients (0%) and 0 of 97 controls (0%)
• Method D: PCR of DNA for XMRV gag, performed by BSRI.
  
• Result: 0 of 50 patients (0%) and 0 of 56 controls (0%)

5. van Kuppeveld et al 2010 "Dutch study"

• Patients: Oxford Criteria
  
• Origin: Netherlands. Recruited and samples taken 1991-1992
  
• Method: PCR of cDNA from PBMCs for XMRV integrase and gag
  
• Result: 0 of 32 patients (0%), 0 of 43 controls (0%)
  

Published Papers - Prostate Cancer

6. Urisman et al 2006

• Patients: Familial Prostate Cancer
• Origin: Cleveland, USA
• Method: PCR on prostate cell DNA
  
• Result: 9 of 86 (10.4%); associated with R462Q QQ genotype

7. Schlaberg et al 2009

• Patients: Prostate Cancer
• Origin: Columbia University Medical Center, USA
  
• Method A: PCR on prostate cell DNA
  
• Results: 14/223 prostate cancer patients (6.2%), 2/101 non-cancer prostate controls (2.0%). Not associated with R462Q QQ genotype.
• Method B: XMRV protein expression (cell reactivity to anti-XMRV serum)
  
• Results: XMRV protein expression in 54/223 (23%) cases with prostate cancer and in 4/101 (4%) controls. Not associated with R462Q QQ genotype.

8. Hohn et al 2009

• Patients: Prostate Cancer
  
• Origin: Berlin, Germany
• Method: PCR on prostate cell DNA
  
• Result: 0 out of 589 (0%)
• Method: Serum immunoreactivity to XMRV proteins (gp70 and Gag)
  
• Result: 0 out of 146 patients, 0 out of 5 controls (0%)
  

9. Fischer et al 2008

• Patients: Non-familial Prostate Cancer
• Origin: Hamburg, Germany
• Method: PCR of prostate cell RNA
• Results: 1/105 patients (0.95%), 1/70 healthy controls (1.42%).
  

Unpublished Data

10. D'Arcy et al 2008

• Patients: Prostrate Cancer
• Origin: Dublin, Ireland
  
• Method A: PCR of prostate cell RNA
• Results: 0 out of 9 (7 R462Q QQ genotype, 2 others) (0%)
  
• Notes: Unpublished data presented at a conference.

11. Furata et al 2009

• Patients: n/a
• Origin: Japan
• Method: "antibodies [to XMRV]"
• Result: 5/300 controls (healthy blood donors) (1.5%)
• Note: Unpublished data presented at a conference - I can't access the abstract and am relying on Erlwein et al's summary. In the light of Groom et al, we really need to know whether the antibodies were truly specific to XMRV.

12. "The Harvey Alter NIH/FDA Paper"

• Patients: CFS?
• Origin: ?
• Method: ?
• Result: "We (FDA & NIH) have independently confirmed the Lombardi group findings." according to a conference presentation by Harvey Alter: see here.
• Notes: Rumored as of 5th July 2010 to be about to appear in PNAS.

13. Qui et al 2010

• Patients: n/a
• Origin: U.S. blood donors
• Method: Blood immunoreactivity to XMRV env, gag, and p15E.
• Result: "reactivity to all 3 antigens in a low proportion (~0.1%) of US blood donors." n=?
  
• Notes: Conference presentation given at the 17th Conference on Retroviruses and Opportunistic Infections 2010.

Harriet Groom, et al. (2010). Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome Retrovirology

Chronic Fatigue Syndrome in "not caused by single virus" shock!

Late last year, Science published a bombshell - Lombardi et al's Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. This paper reported the presence of a recently-discovered virus in 67% of the blood samples from 101 people with chronic fatigue syndrome (CFS).

The question of whether people with CFS are suffering from an organic illness, or whether their condition is partially or entirely psychological in nature, is the Israel vs. Palestine of modern medicine - as a brief look at the Wikipedia talk pages will show. So when Lombardi et al linked CFS to xenotropic murine leukaemia virus-related virus (XMRV), they were hailed as heroes by some, less so by others. For some balanced coverage of this paper, see virology blog. Everyone agreed though that Lombardi et al was, as the saying goes, "important if true"...

But it wasn't, at least not everywhere, according to a paper out today in PLoS ONE: Erlwein et al's Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome. The findings are all there in the title - unlike Lombardi et al, these researchers didn't find XMRV in the blood of any of their blood samples from 186 CFS patients.

Still, before people start proclaiming that the original finding has been "debunked", or decrying these results as flawed, some things to bear in mind...

This was a different country. Erlwein et al used patients attending the CFS clinic at King’s College Hospital, London, England. The patients in the original study were drawn from various parts of the USA. So the new results don't mean that the original findings were wrong, merely that they don't apply everywhere. Notably, XMRV has previously been detected in prostrate cancer cells from American patients, but not European ones, so geographic differences seem to be at work. So maybe XMRV does cause CFS, it's just that the virus doesn't exist in Europe, for whatever reason - but bear in mind that even the original study never showed causation, only a correlation. There are many viruses that infect people in certain parts of the world and don't cause illness.

On the other hand, it was a similar group of patients in terms of symptoms: Diagnosing CFS can be difficult, as there are no biological tests to confirm the condition, but Erlwein et al say that

Both studies use the widely accepted 1994 clinical case definition of CFS. Lombardi et al. reported that their cases ‘‘presented with severe disability’’ and we provide quantifiable evidence confirming high levels of disability in our subjects. Our subjects were also typical of those seen in secondary and tertiary care in other centres.

But the first study selected patients with "immunological abnormalities", although we're given few details...

These are patients that have been seen in private medical practices, and their diagnosis of CFS is based upon prolonged disabling fatigue and the presence of cognitive deficits and reproducible immunological abnormalities. These included but were not limited to perturbations of the 2-5A synthetase/RNase L antiviral pathway, low natural killer cell cytotoxicity (as measured by standard diagnostic assays), and elevated cytokines particularly interleukin-6 and interleukin-8.

The biological methods were similar: Both studies used a standard technique called nested PCR. (Lombardi et al also used various other methods, but their headline finding of XMRV in 67% of CFS patients vs just 4% of health people came from nested PCR.) PCR is a way of greatly increasing the amount of a certain sequence of DNA in a sample. If there's even a little bit to start with, you end up with lots. If there's none, you end up with none. It's easy to tell the difference between lots and none.

But there were some differences. The first study only looked at a certain kind of white blood cells, whereas the new study used DNA from whole blood. Also, the first study targeted a larger span of viral DNA - from 419 to 1154:

For identification of gag, 419F and 1154R were used as forward and reverse primers.

Than the second one, which examined the section between positions 411 and 606. As a result, primer sequences used - which determine the DNA detected - were different. However, the authors of the new study claim that they would definitely have detected XMRV DNA if it had been there, because they used the same methods on control samples with the virus added, and got positive results...

The positive control was a dilution of a plasmid with a full-length XMRV (isolate VP62) insert, generously gifted by Dr R. Silverman.

Silverman was one of the authors of the original paper - so hopefully, both research teams were studying the same virus. But (although I'm no virologist) it seems possible that the new study might have been unable to detect XMRV if the DNA sequence of the virus from British patients was differed at certain key ways - the whole point about nested PCR is that it's extremely specific.

Finally, there are stories behind these papers. The first study, that suggested that XMRV causes CFS, was conducted by the Whittemore Peterson Institute, who firmly believe that CFS is an organic disorder and who are now offering XMRV diagnostic tests to CFS patients. By contrast, the authors of the new study include Simon Wessely, a psychiatrist. Wessely is the most famous (or notorious) advocate of the idea that psychological factors are the key to CFS; he believes that it should be treated with psychotherapy.

I'm sure we'll be hearing a lot more about XMRV in the coming months, so stay tuned.

Erlwein, O., Kaye, S., McClure, M., Weber, J., Wills, G., Collier, D., Wessely, S., & Cleare, A. (2010). Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome PLoS ONE, 5 (1) DOI: 10.1371/journal.pone.0008519

Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, & Mikovits JA (2009). Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science (New York, N.Y.), 326 (5952), 585-9 PMID: 19815723