Abstract

BackgroundIn 2009, a retrospective study reported the detection of xenotropic murine leukemia virus-related virus (XMRV) in clinical isolates derived from individuals with chronic fatigue syndrome or myalgic encephalomyelitis (CFS). While many efforts to confirm this observation failed, one report detected polytropic murine leukemia virus (pMLV), instead of XMRV. In both studies, Polymerase Chain Reaction (PCR)-based methods were employed which could provide the basis for the development of a practical diagnostic tool. To confirm these studies, we hypothesized that the ability to detect these viruses will not only depend upon the technical details of the methods employed but also on the criteria used to diagnose CFS and the availability of well characterized clinical isolates.MethodsA repository of clinical isolates from geographically distinct sites was generated by the collection of fresh blood samples from well characterized CFS and healthy subjects. Molecular techniques were used to generate assay positive controls and to determine the lower limit of detection (LLOD) for murine retroviral and Intracisternal A particle (Cell 12(4):963-72, 1977) detection methods.ResultsWe report the establishment of a repository of well-defined, clinical isolates from five, geographically distinct regions of the US, the comparative determination of the LLODs and validation efforts for the previously reported detection methods and the results of an effort to confirm the association of these retroviral signatures in isolates from individuals with CFS in a blinded, multi-site, prospective study. We detected various, murine retroviral DNA signatures but were unable to resolve a difference in the incidence of their detection between isolates from CFS (5/72; 6.7%) and healthy (2/37; 5.4%) subjects (Fisher’s Exact Test, p-value = 1). The observed sequences appeared to reflect the detection of endogenous murine retroviral DNA, which was not identical to either XMRV or pMLV.ConclusionsWe were unable to confirm a previously reported association between the detection of XMRV or pMLV sequences and CFS in a prospective, multi-site study. Murine retroviral sequences were detected at a low frequency that did not differ between CFS and control subjects. The nature of these sequences appeared to reflect the detection of pre-existing, endogenous, murine retroviral DNA in the PCR reagents employed.

Highlights

  • In 2009, a retrospective study reported the detection of xenotropic murine leukemia virus-related virus (XMRV) in clinical isolates derived from individuals with chronic fatigue syndrome or myalgic encephalomyelitis (CFS)

  • Murine retroviral sequences were detected at a low frequency that did not differ between CFS and control subjects

  • We carefully evaluated the methodologies of the original studies and established the SolveCFS BioBank (SCB); a patient-centered, advocacy-operated, repository of welldefined clinical isolates from geographically distinct regions of the United States

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Summary

Introduction

In 2009, a retrospective study reported the detection of xenotropic murine leukemia virus-related virus (XMRV) in clinical isolates derived from individuals with chronic fatigue syndrome or myalgic encephalomyelitis (CFS). Evidence for the detection of murine leukemia virus (MLV)-related viruses, including XMRV, in isolates derived from patients with CFS has been reported [1,2] The implications of these findings for patients and the safety of the blood supply generated a global response from academic, regulatory and private institutions. In this study we endeavored to confirm a link between CFS and these viruses, but in a prospective manner with fresh, well-defined clinical isolates To enable this effort, we carefully evaluated the methodologies of the original studies and established the SolveCFS BioBank (SCB); a patient-centered, advocacy-operated, repository of welldefined clinical isolates from geographically distinct regions of the United States. The establishment and initial characterization of the SCB should prove to be a valuable reference and tool for the future discovery of CFS-related biomarkers

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