Scientific news update – October

Peter M. Ellery, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Road, Cambridge, CB2 0SP

In this feature, the Science and Technology editorial team aims to review an important current paper in one of the high-impact, non-clinical scientific journals. This month, we examine the latest contribution to the ongoing debate about the aetiology of chronic fatigue syndrome.

Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors
Lo S-C et al. Proc Natl Acad Sci USA. 2010.

What’s the paper about?

In this study, the authors present evidence that gene sequences from a certain type of retrovirus are found more frequently in patients with chronic fatigue syndrome than amongst control subjects from the general population. Lo and colleagues used PCR assays to examine DNA and RNA from the peripheral blood of patients with chronic fatigue syndrome (CFS), and healthy controls. They noted that a certain sequence from a murine leukaemia virus (MLV)-like virus was found in 32/37 (86.5%) CFS patients, but only 3/44 (6.8%) controls, a statistically significant association.

Why is this an important topic?

Chronic fatigue syndrome is a highly debilitating illness. It’s common, affecting perhaps 17 million people worldwide (Lombardi et al, 2009). Initially, its existence was regarded with scepticism by some doctors, but it is now established as a genuine condition, with documented immunological and neurological impairments (Komaroff et al, 2006). The cause is unknown, and discovering more about the aetiology would be an important first step towards developing a cure.

Hang on…doesn’t this all sound familiar?

Many infectious aetiologies have been suggested for CFS in the past, but none with much supporting evidence. However, much excitement came with the publication of a paper in Science in 2009, suggesting an association between xenotropic murine leukaemia virus related-virus (XMRV) and CFS (Lombardi et al, 2009). Despite the researchers’ apparently sound methodology, enthusiasm for the idea was dampened when four subsequent groups failed to replicate the results.

So what does Lo’s paper contribute to the story?

These authors’ findings suggest the presence not of XMRV, but of a similar virus, MLV-like virus. This is another murine retrovirus, which they propose is a subset of XMRV. This may account for the conflicting results of different groups in whether viral DNA was found.
Why should we believe the current authors?

One of the major questions in this story is whether the presence of retroviral DNA in the original study was due to contamination of their samples. Lo’s paper contains several safeguards against this. All positive samples were tested for the presence of mouse mitochondrial DNA using a sensitive PCR assay. Additionally, a selection of the CFS patients who had originally given blood for the study were followed up 15 years after the original samples were taken; after this time, their blood still contained evidence of viral DNA.

What happens next?

Despite showing an association between the virus and the disease, the literature so far tells us nothing further about the nature of their relationship. Is CFS caused by a retrovirus, or is murine retroviral infection a consequence of immune suppression in CFS? Is the virus actually infecting these patients – no group has yet shown integration of viral genetic material into the host genome. Answering these questions will be the next step in improving our understanding of this mysterious condition.

References

Komaroff AL, (2006). Is human herpesvirus-6 a trigger for chronic fatigue syndrome? Journal of Clinical Virology 37 Suppl. 1 S39–S46

Lombardi VC et al., (2009). Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome. Science 326:585-589