scholarly journals Failure to Detect XMRV-Specific Antibodies in the Plasma of CFS Patients Using Highly Sensitive Chemiluminescence Immunoassays

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Brendan Oakes ◽  
Xiaoxing Qiu ◽  
Susan Levine ◽  
John Hackett ◽  
Brigitte T. Huber

In 2009, Lombardi et al. reported their startling finding that the gammaretrovirus xenotropic murine leukemia virus-related retrovirus (XMRV) is present in 67% of blood samples of patients suffering from chronic fatigue syndrome (CFS), as opposed to only 3.7% of samples from healthy individuals. However, we and others could not confirm these results, using a nested PCR assay. An alternative to this highly sensitive, but contamination-prone, technique is to measure the serological response to XMRV. Thus, we tested the plasma samples from our cohorts of CFS patients and healthy controls for the presence of XMRV-specific antibodies. Using two novel chemiluminescence immunoassays (CMIAs), we show that none of our samples have any XMRV-reactive antibodies. Taken together with our previous findings, we conclude that XMRV is not present in any human individual tested by us, regardless of CFS or healthy control.

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
David E. Kang ◽  
Michael C. Lee ◽  
Jaydip Das Gupta ◽  
Eric A. Klein ◽  
Robert H. Silverman

Xenotropic murine leukemia virus-related virus (XMRV) was first reported in 2006 in a study of human prostate cancer patients with genetic variants of the antiviral enzyme, RNase L. Subsequent investigations in North America, Europe, Asia, and Africa have either observed or failed to detect XMRV in patients (prostate cancer, chronic fatigue syndrome-myalgic encephalomyelitis (CFS-ME), and immunosuppressed with respiratory tract infections) or normal, healthy, control individuals. The principal confounding factors are the near ubiquitous presence of mouse-derived reagents, antibodies and cells, and often XMRV itself, in laboratories. XMRV infects and replicates well in many human cell lines, but especially in certain prostate cancer cell lines. XMRV also traffics to prostate in a nonhuman primate model of infection. Here, we will review the discovery of XMRV and then focus on prostate cancer-related research involving this intriguing virus.


2004 ◽  
Vol 12 (1) ◽  
pp. 5-35 ◽  
Author(s):  
Robert J. Suhadolnik ◽  
Daniel L. Peterson ◽  
Nancy L. Reichenbach ◽  
Gail Roen ◽  
Melodie Metzger ◽  
...  

2004 ◽  
Vol 10 (2) ◽  
pp. 278-285 ◽  
Author(s):  
KIM BUSICHIO ◽  
LANA A. TIERSKY ◽  
JOHN DELUCA ◽  
BENJAMIN H. NATELSON

The degree of neuropsychological dysfunction across multiple domains was examined in individuals suffering from chronic fatigue syndrome (CFS). In this descriptive study, a similar series of neuropsychological tests was administered to a group of CFS patients and healthy participants. More specifically, CFS patients (n = 141) who met the 1994 Case Definition criteria were compared to 76 healthy control participants on tests of memory, attention (concentration), speed of information processing, motor speed, and executive functioning. On the 18 measures administered, CFS patients scored 1 standard deviation below the healthy mean on nine measures and scored 2 standard deviations below the healthy mean on four of the measures. Moreover, results indicated that CFS patients were more likely than healthy controls to fail (1.6 SD below the healthy mean) at least one test in each of the following domains: attention, speed of information processing, and motor speed, but not on measures of memory and executive functioning. Finally, CFS patients demonstrated a greater total number of tests failed across domains. (JINS, 2004, 10, 278–285.)


2012 ◽  
Vol 93 (5) ◽  
pp. 915-924 ◽  
Author(s):  
Harriet C. T. Groom ◽  
Kate N. Bishop

In 2006, a new retrovirus was isolated from prostate cancer patient tissue. Named xenotropic murine leukemia virus-related virus (XMRV), this was potentially the third class of retrovirus to be pathogenic in humans. XMRV made a more dramatic impact on the wider scientific community, and indeed the media, in 2009 when it was reported to be present in a remarkably high proportion of patients with chronic fatigue syndrome as well as a significant, albeit smaller, proportion of healthy controls. The apparent strong link to disease and the fear of a previously unknown retrovirus circulating in the general population lead to a surge in XMRV research. Subsequent studies failed to find an association of XMRV with disease and, in most cases, failed to find the virus in human samples. In 2011, the case against XMRV and human disease strengthened, ending with several decisive publications revealing the origin of the virus and demonstrating contamination of samples. In this review, we outline the passage of research on XMRV and its potential association with disease from its isolation to the present day, where we find ourselves at the end of a turbulent story.


2010 ◽  
Vol 84 (22) ◽  
pp. 11970-11980 ◽  
Author(s):  
Yuhe Yan ◽  
Qingping Liu ◽  
Kurt Wollenberg ◽  
Carrie Martin ◽  
Alicia Buckler-White ◽  
...  

ABSTRACT Genetic conflicts between retroviruses and their receptors result in the evolution of novel host entry restrictions and novel virus envelopes, and such variants can influence trans-species transmission. We screened rodents and other mammals for sequence variation in the Xpr1 receptor for the mouse xenotropic or polytropic mouse leukemia viruses (X-MLVs or P-MLVs, respectively) of the gammaretrovirus family and for susceptibility to mouse-derived X/P-MLVs and to XMRV (xenotropic murine leukemia virus-related virus), an X-MLV-like virus isolated from humans with prostate cancer and chronic fatigue syndrome. We identified multiple distinct susceptibility phenotypes; these include the four known Xpr1 variants in Mus and a novel fifth Xpr1 gene found in Mus molossinus and Mus musculus. We describe the geographic and species distribution of the Mus Xpr1 variants but failed to find the X-MLV-restrictive laboratory mouse allele in any wild mouse. We used mutagenesis and phylogenetic analysis to evaluate the functional contributions made by constrained, variable, and deleted residues. Rodent Xpr1 is under positive selection, indicating a history of host-pathogen conflicts; several codons under selection have known roles in virus entry. All non-Mus mammals are susceptible to mouse X-MLVs, but some restrict other members of the X/P-MLV family, and the resistance of hamster and gerbil cells to XMRV indicates that XMRV has unique receptor requirements. We show that the hypervariable fourth extracellular XPR1 loop (ECL4) contains three evolutionarily constrained residues that do not contribute to receptor function, we identify two novel residues important for virus entry (I579 and T583), and we describe a unique pattern of ECL4 variation in the three virus-restrictive Xpr1 variants found in MLV-infected house mice; these mice carry different deletions in ECL4, suggesting either that these sites or loop size affects receptor function.


mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Harvey J. Alter ◽  
Judy A. Mikovits ◽  
William M. Switzer ◽  
Francis W. Ruscetti ◽  
Shyh-Ching Lo ◽  
...  

ABSTRACT The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. IMPORTANCE Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated prevalence of 42/10,000 in the United States, with annual direct medical costs of $7 billion. Here, the original investigators who found XMRV and pMLV (polytropic murine leukemia virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects. The increasing frequency with which molecular methods are used for pathogen discovery poses new challenges to public health and support of science. It is imperative that strategies be developed to rapidly and coherently address discoveries so that they can be carried forward for translation to clinical medicine or abandoned to focus resource investment more productively. Our study provides a paradigm for pathogen dediscovery that may be helpful to others working in this field.


2010 ◽  
Vol 202 (10) ◽  
pp. 1478-1481 ◽  
Author(s):  
Timothy J. Henrich ◽  
Jonathan Z. Li ◽  
Donna Felsenstein ◽  
Camille N. Kotton ◽  
Robert M. Plenge ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document