No Evidence of XMRV in prostate cancer cohorts in the Midwestern United States

Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Retrovirology (Impact Factor: 4.19). 03/2011; 8(1):23. DOI: 10.1186/1742-4690-8-23
Source: PubMed


Xenotropic murine leukemia virus (MLV)-related virus (XMRV) was initially identified in prostate cancer (PCa) tissue, particularly in the prostatic stromal fibroblasts, of patients homozygous for the RNASEL R462Q mutation. A subsequent study reported XMRV antigens in malignant prostatic epithelium and association of XMRV infection with PCa, especially higher-grade tumors, independently of the RNASEL polymorphism. Further studies showed high prevalence of XMRV or related MLV sequences in chronic fatigue syndrome patients (CFS), while others found no, or low, prevalence of XMRV in a variety of diseases including PCa or CFS. Thus, the etiological link between XMRV and human disease remains elusive. To address the association between XMRV infection and PCa, we have tested prostate tissues and human sera for the presence of viral DNA, viral antigens and anti-XMRV antibodies.
Real-time PCR analysis of 110 PCa (Gleason scores >4) and 40 benign and normal prostate tissues identified six positive samples (5 PCa and 1 non-PCa). No statistical link was observed between the presence of proviral DNA and PCa, PCa grades, and the RNASEL R462Q mutation. The amplified viral sequences were distantly related to XMRV, but nearly identical to endogenous MLV sequences in mice. The PCR positive samples were also positive for mouse mitochondrial DNA by nested PCR, suggesting contamination of the samples with mouse DNA. Immuno-histochemistry (IHC) with an anti-XMRV antibody, but not an anti-MLV antibody that recognizes XMRV, sporadically identified antigen-positive cells in prostatic epithelium, irrespectively of the status of viral DNA detection. No serum (159 PCa and 201 age-matched controls) showed strong neutralization of XMRV infection at 1:10 dilution.
The lack of XMRV sequences or strong anti-XMRV neutralizing antibodies indicates no or very low prevalence of XMRV in our cohorts. We conclude that real-time PCR- and IHC-positive samples were due to laboratory contamination and non-specific immune reactions, respectively.

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    • "An important finding in 2009 was that the cell line 22Rv1, derived from a human PC patient, harbored multiple copies of XMRV DNA and expressed it highly.32 However, other subsequent studies failed to detect XMRV in prostate tissue, serum or peripheral blood mononuclear cells (PBMC) of patients with PC from the United States and Europe.33,34,35,36,37,38 "
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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).
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    • "Primers for UIF were 5'-ATGAACCGGTTTGGTACCCGG-3' and 5'-CTATCCCACGGTGACAAAGCG-3', and GAPDH was amplified by 5'-GTCCATGCCATCACTGCCA-3' and 5'-TTACTCCTTGGAGGCCAT-3'. The real-time qPCR assay was performed as described previously [48,49]. For global gene expression analysis, all the probes and primers were purchased from IDT (Coralville, IA, USA). "
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    • "In a study the absence of XMRV DNA or neutralizing anti-XMRV antibodies suggests no or very low prevalence of XMRV in their cohorts. They conclude that real-time PCR and IHC positive samples were laboratory contamination and falsepositive immune reactions (Sakuma et al., 2011). Our PCR result in specimens was negative for XMRV and related MLV, but only YAC-1 cells was positive for MLV; thus we did not have any mouse cross contamination. "
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