Failure to detect Xenotropic murine leukaemia virus-related virus in Chinese patients with chronic fatigue syndrome

Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Virology Journal (Impact Factor: 2.18). 09/2010; 7(1):224. DOI: 10.1186/1743-422X-7-224
Source: PubMed


Recent controversy has surrounded the question of whether xenotropic murine leukaemia virus-related virus (XMRV) contributes to the pathogenesis of chronic fatigue syndrome (CFS). To investigate the question in a Chinese population, 65 CFS patients and 85 blood donor controls were enrolled and multiplex real-time PCR or reverse transcriptase PCR (RT-PCR) was developed to analyze the XMRV infection status of the study participants. The assay was standardized by constructing plasmid DNAs and armored RNAs as XMRV standards and competitive internal controls (CICs), respectively.
The sensitivities of the multiplex real-time PCR and RT-PCR assays were 20 copies/reaction and 10 IU/ml, respectively, with 100% specificity. The within-run precision coefficient of variation (CV) ranged from 1.76% to 2.80% and 1.70% to 2.59%, while the between-run CV ranged from 1.07% to 2.56% and 1.06% to 2.74%. XMRV was not detected in the 65 CFS patients and 65 normal individuals out of 85 controls.
This study failed to show XMRV in peripheral blood mononuclear cells (PBMCs) and plasma of Chinese patients with CFS. The absence of XMRV nucleic acids does not support an association between XMRV infection and the development of CFS in Chinese.

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    • "Despite these early reports and the excitement they generated in the CFS patient community, the association of XMRV with CFS has been disproven. Many studies have failed to detect XMRV in CFS cohorts around the globe.27,41,42,43,44,45,46,47,48,49,50,51,52 Surveys also have not identified XMRV infection in the general human population 53,54,55,56 or in humans at high risk for viral infections (e.g., HIV-1-infected individuals).57,58,59,60,61,62 "
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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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    • "Currently, XMRV infection and replication is quantified by measuring proviral DNA numbers in infected cell cultures, or by determining virion associated genomic RNA copy numbers and reverse transcriptase activities in the supernatants of infected cells [24,25,36,37]. Alternatively, productive infection with release of infectious XMRV has also been analyzed by titrating progeny virus on reporter cell lines [26,38]. "
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    ABSTRACT: The gammaretrovirus termed xenotropic murine leukemia virus-related virus (XMRV) was described to be isolated from prostate cancer tissue biopsies and from blood of patients suffering from chronic fatigue syndrome. However, many studies failed to detect XMRV and to verify these disease associations. Data suggesting the contamination of specimens in particular by PCR-based methods and recent reports demonstrating XMRV generation via recombination of two murine leukemia virus precursors raised serious doubts about XMRV being a genuine human pathogen. To elucidate cell tropism of XMRV, we generated replication competent XMRV reporter viruses encoding a green fluorescent protein or a secretable luciferase as tools to analyze virus infection of human cell lines or primary human cells. Transfection of proviral DNAs into LNCaP prostate cancer cells resulted in readily detectably reporter gene expression and production of progeny virus. Inoculation of known XMRV susceptible target cells revealed that these virions were infectious and expressed the reporter gene, allowing for a fast and highly sensitive quantification of XMRV infection. Both reporter viruses were capable of establishing a spreading infection in LNCaP and Raji B cells and could be easily passaged. However, after inoculation of primary human blood cells such as CD4 T cells, macrophages or dendritic cells, infection rates were very low, and a spreading infection was never established. In line with these results we found that supernatants derived from these XMRV infected primary cell types did not contain infectious virus. Thus, although XMRV efficiently replicated in some human cell lines, all tested primary cells were largely refractory to XMRV infection and did not support viral spread. Our results provide further evidence that XMRV is not a human pathogen.
    PLoS ONE 09/2013; 8(9):e74427. DOI:10.1371/journal.pone.0074427 · 3.23 Impact Factor
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    • "XMRV was also not or rarely detected in general populations worldwide. Only about 1% of control groups were found to be positive for XMRV in Germany [10], the U.K [12] and Japan [30], but no XMRV was detected in Chinese blood donors [31]. Negative results were reported for XMRV testing of blood donors or individuals infected HIV-1 in Africa [22]. "
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    ABSTRACT: Preliminary studies in chronic fatigue syndrome (CFS) patients and XMRV infected animals demonstrated plasma viremia and infection of blood cells with XMRV, indicating the potential risk for transfusion transmission. XMRV and MLV-related virus gene sequences have also been detected in 4-6% of healthy individuals including blood donors in the U.S. These results imply that millions of persons in the U.S. may be carrying the nucleic acid sequences of XMRV and/or MLV-related viruses, which is a serious public health and blood safety concern. To gain evidence of XMRV or MLV-related virus infection in the U.S. blood donors, 110 plasma samples and 71 PBMC samples from blood donors at the NIH blood bank were screened for XMRV and MLV-related virus infection. We employed highly sensitive assays, including nested PCR and real-time PCR, as well as co-culture of plasma with highly sensitive indicator DERSE cells. Using these assays, none of the samples were positive for XMRV or MLV-related virus. Our results are consistent with those from several other studies, and demonstrate the absence of XMRV or MLV-related viruses in the U.S. blood donors that we studied.
    PLoS ONE 11/2011; 6(11):e27391. DOI:10.1371/journal.pone.0027391 · 3.23 Impact Factor
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