No Evidence of Murine-Like Gammaretroviruses in CFS Patients Previously Identified as XMRV-Infected

Wisconsin Viral Research Group, Milwaukee, WI 53226, USA.
Science (Impact Factor: 33.61). 06/2011; 333(6038):94-7. DOI: 10.1126/science.1204963
Source: PubMed


Members of the gammaretroviruses--such as murine leukemia viruses (MLVs), most notably XMRV [xenotropic murine leukemia virus (X-MLV)-related virus--have been reported to be present in the blood of patients with chronic fatigue syndrome (CFS). We evaluated blood samples from 61 patients with CFS from a single clinical practice, 43 of whom had previously been identified as XMRV-positive. Our analysis included polymerase chain reaction and reverse transcription polymerase chain reaction procedures for detection of viral nucleic acids and assays for detection of infectious virus and virus-specific antibodies. We found no evidence of XMRV or other MLVs in these blood samples. In addition, we found that these gammaretroviruses were strongly (X-MLV) or partially (XMRV) susceptible to inactivation by sera from CFS patients and healthy controls, which suggested that establishment of a successful MLV infection in humans would be unlikely. Consistent with previous reports, we detected MLV sequences in commercial laboratory reagents. Our results indicate that previous evidence linking XMRV and MLVs to CFS is likely attributable to laboratory contamination.

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Available from: Allyn Knox, Aug 05, 2014
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    • "Therefore, we designed a novel SMIA based on several metal labels using anodic and cathodic stripping voltammetry, which was designated as a bidirectional voltammetry. Moreover, the highly sensitive detection of trace target analytes has been required in early clinical diagnosis [26] [27]. In order to enhance the sensitivity significantly, various polymerization-based amplification systems have been built as matrix by immobilizing signal source material. "
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    ABSTRACT: A novel bidirectional (anodic and cathodic) stripping voltammetric immunoassay (SVI) was designed for the simultaneous determination of multiple model cancer biomarkers (AFP, CEA and CA19-9) in a single run, based on the integration of Envision complex loaded metal nanoparticles as signal tags and immunomagnetic beads as capture probes. The Envision complex, which is a long branching polymer consisting of numerous secondary antibodies and horseradish peroxidase (HRP), was employed for signal amplification by labeling corresponding detection antibodies and further loading metal nanoparticles (CdS, PbS and gold) to prepare distinguishable metal signal tags. Herein, the generation of immunosensing probes involved the co-immobilization of three types of primary anti-AFP, anti-CEA, and anti-CA19-9 antibodies onto a single magnetic Dynabead. After a two-binding step sandwich-type immunoassay, the Envision/CdS, Envision/PbS and Envision/Au signal tags were introduced onto the surface of the Dynabeads. The subsequent bidirectional voltammetric analysis of stripping metal components from immunocomplexes for quantification of tumor biomarkers was performed in a microcell with minimum capacity of 50 mu L. Experimental results showed the immunoassay enabled the simultaneous determination of multiple biomarkers over a broad range of concentrations (AFP, 1 pg mL(-1)-50 ng mL(-1); CEA, 1 pg mL(-1)-50 ng mL(-1); CA19-9, 5 pg mL(-1)-100 ng mL(-1)) with detection limits reaching 0.02 pg mL(-1) for AFP, 0.05 pg mL(-1) for CEA, and 0.3 pg mL(-1) for CA19-9. The results indicated that the proposed bidirectional multiplexed immunoassay can increase the number of analytes by SVI and has high sensitivity, excellent stability, and great promise for applications in clinical cancer diagnosis.
    Sensors and Actuators B Chemical 07/2014; 197:244–253. DOI:10.1016/j.snb.2014.03.011 · 4.10 Impact Factor
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    • "Subsequently, many of the tumor samples initially reported to be XMRV positive were re-analyzed and found to be contaminated with the VP62 XMRV plasmid or 22Rv1 cells,28,70 leading to an initial partial retraction of the paper by the authors.71 A large-scale collaborative blinded analysis27 tested PBMCs of CFS patients in independent laboratories and led to the conclusion that the initial reports of XMRV in the general population also resulted from laboratory contamination, or from incorrect initial identification of positive samples due in part to contaminating mouse DNA in PCR reagents.72,73 Subsequently, the key papers reporting discovery of XMRV and its association with PC or CFS25,39,40 were retracted.71,74 "
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    ABSTRACT: Xenotropic murine leukemia virus-related virus (XMRV) was discovered in 2006 in a search for a viral etiology of human prostate cancer (PC). Substantial interest in XMRV as a potentially new pathogenic human retrovirus was driven by reports that XMRV could be detected in a significant percentage of PC samples, and also in tissues from patients with chronic fatigue syndrome (CFS). After considerable controversy, etiologic links between XMRV and these two diseases were disproven. XMRV was determined to have arisen during passage of a human PC tumor in immunocompromised nude mice, by activation and recombination between two endogenous murine leukemia viruses from cells of the mouse. The resulting XMRV had a xentropic host range, which allowed it replicate in the human tumor cells in the xenograft. This review describes the discovery of XMRV, and the molecular and virological events leading to its formation, XMRV infection in animal models and biological effects on infected cells. Lessons from XMRV for other searches of viral etiologies of cancer are discussed, as well as cautions for researchers working on human tumors or cell lines that have been passed through nude mice, includingpotential biohazards associated with XMRV or other similar xenotropic murine leukemia viruses (MLVs).
    Emerging Microbes and Infections 04/2014; 3(4):e. DOI:10.1038/emi.2014.25 · 2.26 Impact Factor
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    • "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. Proposed reasons to explain the conflicting data are unknown but may be: technical differences, lack of standardized XMRV PCR assays, assay sensitivity, contamination by and cross-reactivity of XMRV PCR assays with closely related endogenous MLVs such as trace quantities of mouse genomic DNA found in reagents and samples (Hue et al., 2010; Oakes et al., 2010; Robinson et al., 2010; Sato et al., 2010; Knox, Carrigan et al., 2011; Tuke et al., 2011), differences in the geographical distribution of XMRV, sequence differences among XMRV genomes (Silverman et al., 2010; Singh et al., 2010; Knox et al., 2011) and factors related to the population genetic factors (Switzer et al., 2011). Due to public health and medical consequences of potential XMRV or related MLVs infection in humans, we considered it is important to confirm or reject their association with prostate cancer in Iranian context. "
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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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