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

Abstract

*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. X enotropic retroviruses, first discovered in mice, have the unusual characteristic of being endogenous to animal species, i.e., integrated into the animal's genome, but not able to reinfect cells from that species. However, as the name (xenos, foreign) implies, these viruses can infect cells from other animal species. The xenotropic murine leukemia virus (X-MLV), for example, infects cells from several species including humans but cannot infect many mouse cells (1-3). One particular virus within this group, XMRV (xenotropic murine leukemia virus-related virus), was reported to be present in a subset of human prostate tumors (4) and in blood samples from patients with chronic fatigue syndrome (CFS) (5). Other murine-related gammaretroviruses have also reportedly been detected in CFS patients (6). The infection of humans with these viruses is controversial. Investigators evaluating independent cohorts of CFS patients have failed to detect XMRVor other MLVs (7-12), and contamination of human clinical material (13,14) and reagents (e.g., Taq polymerase) (15) with mouse DNA containing MLV-like sequences has been reported.To investigate these discrepancies in a more direct manner, we performed an extensive virological evaluation of blood samples from two human populations with a clinical diagnosis of CFS (16), many of whom had been diagnosed previously as XMRV-infected. The first (P1) consisted of 41 CFS patients ranging in age from 5 to 73 years who came from a private medical practice (Sierra Internal Medicine, Incline Village, Nevada). Twenty-six of the CFS subjects (63%) were female, and 15 (37%) were male; the female median age was 52 years (range 5 to 72 years), and the male median age was 49 years (range 20 to 73 years). These patients were an unselected, sequentially enrolled population submitted for diagnostic testing to the Wisconsin Viral Research Group (WVRG) and w...

No Detection of Xenotropic Murine Leukemia Virus-Related Viruses in Prostate Cancer in Sanandaj, West of Iran

“…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 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.…”

“…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).…”

XMRV ist nicht human-pathogen und hat keine Bedeutung für die Sicherheit von Blut und Blutprodukten

“…In der Mehrzahl der später veröffentlich-ten Studien wurde XMRV jedoch in keiner einzigen Probe nachgewiesen [8,9,10,11,12,13]. Bei Wiederholungsuntersuchungen von zuvor am WPI im Rahmen der initialen Studie [3] positiv getesteten CFS-Patienten konnten in unabhängigen Laboren in keinem einzigen Fall XMRV oder spezifische Antikörper gegen XMRV-Proteine nachgewiesen werden, obwohl nahezu identische, hochsensitive Verfahren verwendet wurden [14,15]. Hiermit stellt sich die Frage, was die Ursache für den beschriebenen Nachweis von XMRV am WPI und an einem kommerziellen Labor sowie in den anderen Studien sein könnte.…”

Xenotropic Murine Leukemia Virus-Related Virus Proviral DNA Not Detected in Blood Samples Donated in Japan

“…Furthermore, XMRV may be the result of a recombination of two MLV ancestors in laboratories (16). In addition to the negative findings in CFS patients (17,18), it was demonstrated that there is no evidence of XMRV infection in blood donors in the USA (19). In Japan, Furuta et al did not detect XMRV in CFS patients (8).…”