Virology research

XMRV mouse retrovirus involvement in ME/CFS controversy

G.Simmons (San Francisco, USA) discussed multi-laboratory evaluations of XMRV detection assays. He presented work investigating the prevalence of XMRV in blood donors. Published work on 22/9/11 in Science Express showed a failure to detect XMRV in any sample. Only one lab found clinical samples to be nucleic acid test (NAT) positive. These positives were not reliable among replicates. Using a number of techniques, there was very little correlation between positives from the original WPI study and other assays. The conclusion was that routine screening of blood donors for XMRV is not warranted.

K.de Meirleir (Brussels, Belgium) detected anti-XMRV antibodies in the serum of patients and healthy blood donors. Of 84 Belgian CFS patients, 21 had developed CFS after receiving a blood transfusion. Controls were 44 healthy blood donors. 57% of CFS patients and 16% of controls tested antibody positive. 10 of the 21 CFS patients who had had a blood transfusion tested positive. PCR was not used. Western blot was used to confirm the serology data. These results were statistically significant. Samples were blinded and analysed at the WPI.

M.Hansen (NY, USA) presented work looking for MLV-like gag sequences in blood and cell lines incubated with plasma from CFS patients and controls. 30 were patients from D.Bell, 24 from S.Levine and 12 controls from Ithaca, NY. No XMRV was detected in the Bell group. Cells were cultured for 30 days—some gag sequences were found but no other retroviral sequences could be found. There were no statistical differences between patients and controls. Everything possible was done to avoid contamination. The Levine samples were all negative for gag sequences. This research is ongoing.

J.Mikovits (Reno, USA) and J.Coffin (Boston, USA) discussed the case for and against human gammaretroviruses in CFS. Mikovits outlined her earlier work involving detection of XMRV. As well as identifying the virus in a significant number of patients, their lab have identified an inflammatory cytokine and chemokinesignature that distinguishes XMRV-infected patients from controls with 94% sensitivity and specificity. Further tests are being developed for detection and characterisation of XMRV. Coffin’s lab had looked hard for XMRV in mice, and did not find it in any mouse strain tested, but found an XMRV ancestor in the mouse genome. A detection assay has been developed. He pointed out that XMRV is a virus and MLV is not a virus, but fragments.

Mice are extremely widespread, and mouse DNA can be found on laboratory surfaces and can contaminate common reagents and materials. Most virologists now consider XMRV to be a consequence of a collection of artifacts originating from endogenous MLVs prevalent in the laboratory. It is likely to be an accidental laboratory creation from the 1990s. It is yet to be worked out how it has got into clinical samples from CFS patients.

ME/CFS after SARS and other immunological findings

Post-SARS Syndrome was outlined by H. Moldofsky (Toronto, Canada). SARS results from infection by a coronavirus A. It creeps into the brain via the olfactory bulb in mice, and possibly via this route in humans. 250 cases occurred in Toronto, transmitted by one person who had been in Hong Kong. There were 44 deaths and 50 cases who remained ill post-SARS. These correlated with a diagnosis of CFS. Sleep was disordered and this was similar to that seen in fibromyalgia syndrome (FMS), but there was a lower rating of the alpha EEG sleep anomaly in post-SARS as compared to FMS. The myalgia was also less severe.

J.Montoya (Stanford, USA) considered the role of the immune response in CFS. Typical pathogens in CFS are involved, and are mostly intracellular. There is initial tropism (e.g., respiratory or GI) followed by involvement of target organs (eglymphatics)). Different pathogens take similar pathways. CFS may be sustained for years, and pathogens reactivate periodically. Reactivation tends to be at low levels. This leads to an immune response, but this is not strong enough to kill the organisms, so the bugs remain latent, and then reactivate again leading to symptoms. CFS is a multi-system disease with phases of immune response.

Peripheral blood studies are useful and convenient but imperfect. Immune abnormalities have been inconsistent across labs, although some are consistent. Inconsistency may be due to host variables, multiple triggers, fluctuating nature of the disease, duration and severity. There are also other non-CFS variables such as methodological variables and statistical issues. There is a need to involve all available data, apply new technology and coordinate research.