Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

Jefferiss Research Trust Laboratories, Section of Infectious Diseases, Wright-Fleming Institute, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, United Kingdom.
PLoS ONE (Impact Factor: 3.53). 01/2010; 5(1):e8519. DOI: 10.1371/journal.pone.0008519
Source: PubMed

ABSTRACT In October 2009 it was reported that 68 of 101 patients with chronic fatigue syndrome (CFS) in the US were infected with a novel gamma retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), a virus previously linked to prostate cancer. This finding, if confirmed, would have a profound effect on the understanding and treatment of an incapacitating disease affecting millions worldwide. We have investigated CFS sufferers in the UK to determine if they are carriers of XMRV.
Patients in our CFS cohort had undergone medical screening to exclude detectable organic illness and met the CDC criteria for CFS. DNA extracted from blood samples of 186 CFS patients were screened for XMRV provirus and for the closely related murine leukaemia virus by nested PCR using specific oligonucleotide primers. To control for the integrity of the DNA, the cellular beta-globin gene was amplified. Negative controls (water) and a positive control (XMRV infectious molecular clone DNA) were included. While the beta-globin gene was amplified in all 186 samples, neither XMRV nor MLV sequences were detected.
XMRV or MLV sequences were not amplified from DNA originating from CFS patients in the UK. Although we found no evidence that XMRV is associated with CFS in the UK, this may be a result of population differences between North America and Europe regarding the general prevalence of XMRV infection, and might also explain the fact that two US groups found XMRV in prostate cancer tissue, while two European studies did not.

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Available from: Simon Wessely, Dec 30, 2013
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    • "XMRV was also reported to be presence in patients with chronic fatigue syndrome (CFS) (Lombardi et al., 2009). However, the link between XMRV and CFS is unclear, because in other studies it has failed to detect XMRV infection in CFS patients (Erlwein et al., 2010; Groom et al., 2010; Switzer et al., 2010; van Kuppeveld et al., 2010; Knox et al., 2011; Satterfield et al., 2011; Shin et al., 2011). However, gammaretroviruses are known to induce cancer in animals, understanding XMRV or related MLV infections in human prostate cancer tissues will shed light on their potential contribution to human disease. "
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    ABSTRACT: Background: Multiple etiologies have been hypothesized for prostate cancer, including genetic defects and infectious agents. A recently reported gamaretrovirus, xenotropic murine leukemia virus-related virus (XMRV) has been reported to be detected in prostate cancer. However, this virus has not been detected in similar groups of patients in other studies. Herein, we sought to detect XMRV in prostate cancers and benign controls in Sanandaj, west of Iran. Materials and Methods: In a case-control study, genomic DNA was extracted from formalin fixed and paraffin embedded prostate tissues from a total of 163 Iranian patients. We developed a conventional and a nested PCR assay using primers targeting to an env specific sequence of XMRV. PCR assays were carried out on 63 prostate cancers and 100 benign prostate hyperplasias. Results: Beta-actin sequences were successfully detected in the DNA extracts from all prostate tissues, confirming DNA extraction integrity. We did not detect XMRV in samples either from prostate cancers or benign prostate hyperplasias using XMRV specific primers. Conclusions: We conclude that in our population XMRV does not play a role in genesis of prostate cancer.
    Asian Pacific journal of cancer prevention: APJCP 11/2013; 14(11):6929-33. DOI:10.7314/APJCP.2013.14.11.6929 · 2.51 Impact Factor
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    • "The broad range of symptoms related to CFS and unpredictability of onset in patients have contributed to confounding results that have made it difficult to pin-point an aetiology, as summarised in recent reviews [3] [4]. More recent contradictions centre around the retrovirus known as Xenotropic Murine Leukaemia Virus-Related Virus, and Lombardi et al. [5] found a high infection rate in CFS sufferers that has since been supported [6] and disputed [7]. Another potential causal factor in eliciting CFS-related symptoms has been hypothesised to be gut dysbiosis [8]. "
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    ABSTRACT: Chronic fatigue syndrome (CFS) is a debilitating multisystem disorder characterised by long-term fatigue with a variety of other symptoms including cognitive dysfunction, unrefreshing sleep, muscle pain, and post-exertional malaise. It is a poorly understood condition that occurs in ~5 in every 1000 individuals. We present here a preliminary study on the analysis of blood samples from 11 CFS and 10 control subjects through NMR metabolic profiling. Identified metabolites that were found to be significantly altered between the groups were subjected to correlation analysis to potentially elucidate disturbed metabolic pathways. Our results showed a significant reduction of glutamine (P=0.002) and ornithine (P<0.05) in the blood of the CFS samples. Correlation analysis of glutamine and ornithine with other metabolites in the CFS sera showed relationships with glucogenic amino acids and metabolites that participate in the urea cycle. This indicates a possible disturbance to amino acid and nitrogen metabolism. It would be beneficial to identify any potential biomarkers of CFS for accurate diagnosis of the disorder.
    Clinica chimica acta; international journal of clinical chemistry 06/2012; 413(19-20):1525-31. DOI:10.1016/j.cca.2012.06.022 · 2.76 Impact Factor
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    • "For example, Arnold et al. detected anti- XMRV antibodies in 27% of individuals with prostate cancer [10], Schlaberg et al. found XMRV nucleic acid in 23% of prostate cancers and 4% of controls [11], and Danielson et al. detected XMRV in 22.8% of extracted prostate tissues from individuals who had radical prostatectomies [12]. However, controversy arose when other laboratories could not demonstrate comparable findings in similar cohorts not only in the US [13] but in Germany [14], The Netherlands [15], and England [16] [17]. Adding to the controversy, Lo et al. reported the presence of mouse retroviral sequences, but not XMRV, in 86.5% of CFS patients [18]. "
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    ABSTRACT: The MLV-related retrovirus, XMRV, was recently identified and reported to be associated with both prostate cancer and chronic fatigue syndrome. At the National Cancer Institute-Frederick, MD (NCI-Frederick), we developed highly sensitive methods to detect XMRV nucleic acids, antibodies, and replication competent virus. Analysis of XMRV-spiked samples and/or specimens from two pigtail macaques experimentally inoculated with 22Rv1 cell-derived XMRV confirmed the ability of the assays used to detect XMRV RNA and DNA, and culture isolatable virus when present, along with XMRV reactive antibody responses. Using these assays, we did not detect evidence of XMRV in blood samples (N = 134) or prostate specimens (N = 19) from two independent cohorts of patients with prostate cancer. Previous studies detected XMRV in prostate tissues. In the present study, we primarily investigated the levels of XMRV in blood plasma samples collected from patients with prostate cancer. These results demonstrate that while XMRV-related assays developed at the NCI-Frederick can readily measure XMRV nucleic acids, antibodies, and replication competent virus, no evidence of XMRV was found in the blood of patients with prostate cancer.
    Advances in Virology 11/2011; 2011:272193. DOI:10.1155/2011/272193
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