Analysis of cerebrospinal fluid from chronic fatigue syndrome patients for multiple human ubiquitous viruses and xenotropic murine leukemia‐related virus

@article{Schutzer2011AnalysisOC,
  title={Analysis of cerebrospinal fluid from chronic fatigue syndrome patients for multiple human ubiquitous viruses and xenotropic murine leukemia‐related virus},
  author={Steven E. Schutzer and Megan A. Rounds and B. H. Natelson and David J. Ecker and Mark W. Eshoo},
  journal={Annals of Neurology},
  year={2011},
  volume={69}
}
Recent reports showed many patients with chronic fatigue syndrome (CFS) harbor a retrovirus, xenotropic murine leukemia‐related virus (XMRV), in blood; other studies could not replicate this finding. A useful next step would be to examine cerebrospinal fluid, because in some patients CFS is thought to be a brain disorder. Finding a microbe in the central nervous system would have greater significance than in blood because of the integrity of the blood–brain barrier. We examined cerebrospinal… 

Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome

A markedly disturbed immune signature in the cerebrospinal fluid of cases is indicated that is consistent with immune activation in the central nervous system, and a shift toward an allergic or T helper type-2 pattern associated with autoimmunity is indicated.

XMRV: Emerging Human Infection or False Alarm

The relationship of XMRV with these diseases became doubtful due to evidence of laboratory and reagent contamination, potentially escaped laboratory viruses and plasmids, and nonreproducibility of the findings.

No evidence of XMRV provirus sequences in patients with myalgic encephalomyelitis/chronic fatigue syndrome and individuals with unspecified encephalopathy.

Using nPCR, there is no evidence of XMRV infection either in apparently healthy individuals or in patients with ME/CFS and individuals with unspecified encephalopathy.

No association found between the detection of either xenotropic murine leukemia virus-related virus or polytropic murine leukemia virus and chronic fatigue syndrome in a blinded, multi-site, prospective study by the establishment and use of the SolveCFS BioBank

A repository of well-defined, clinical isolates from five, geographically distinct regions of the US, the comparative determination of the LLODs and validation efforts for the previously reported detection methods, and the results of an effort to confirm the association of these retroviral signatures in isolate from individuals with CFS in a blinded, multi-site, prospective study are reported.

Restricted Replication of Xenotropic Murine Leukemia Virus-Related Virus in Pigtailed Macaques

Findings indicate that XMRV replication and spread were limited in pigtailed macaques, predominantly by APOBEC-mediated hypermutation.

Chronic Fatigue Syndrome and Viral Infections

This immunological procedure was also used in 1975 by Yvonne Cossart to detect human parvovirus B19 in the serum of a blood donor in London (Cossart et al., 1975).

Extraordinary claims require extraordinary evidence

The focus of research into CFS has been to investigate possible viral or immune causes, and a new virus claim appeared: xenotropic murine leukemia virus-related virus or XMRV, which offered a simple, clear and reasonable explanation for their symptoms and provided reassurance that they had a true illness and not a psychological condition.

Gene Expression in Chronic Fatigue Syndrome

Research has demonstrated that CFS impacts the endocrine, neurological, immune and metabolic processes resulting in impaired physiological homeostasis and while these processes are likely compromised and collectively contribute to ill health in CFS patients, CFS remains a disorder lacking a clear molecular or biochemical cause.

References

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Xenotropic murine leukemia virus-related virus prevalence in patients with chronic fatigue syndrome or chronic immunomodulatory conditions.

It is found that there is no association between XMRV and patients with chronic fatigue syndrome or chronic immunomodulatory conditions.

Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

Although it was reported that 68 of 101 patients with chronic fatigue syndrome in the US were infected with a novel gamma retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), a virus previously linked to prostate cancer, no evidence that XMRV is associated with CFS in the UK is found.

Failure to detect xenotropic murine leukemia virus-related virus in blood of individuals at high risk of blood-borne viral infections.

XMRV was not enriched in patients with blood-borne or sexually transmitted infections from the United Kingdom and Western Europe, and was undetectable in plasma or peripheral blood mononuclear cells by polymerase chain reaction targeting XMRV gag or env.

PCR and serology find no association between xenotropic murine leukemia virus-related virus (XMRV) and autism

None of the PCR assays found any evidence of XMRV infection in blood cells from patients or controls, and no anti-XMRV antibodies were detected, ruling out possible low level or abortive infections in blood or in other reservoirs.

Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors

The gag and env sequences from CFS patients were more closely related to those of polytropic mouse endogenous retroviruses than to those that of XMRVs and were even less closely related than those of ecotropic MLVs, which is a genetically diverse group of MLV-related viruses.

No evidence for XMRV association in pediatric idiopathic diseases in France

This investigation investigated the presence of XMRV in a selection of pediatric idiopathic infectious diseases with symptoms that are suggestive of a retroviral infection, as well as in children with respiratory diseases and in adult patients with spondyloarthritis, indicating that X MRV is not involved in these pathologies.

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome

The results indicate that PCR from DNA of unstimulated peripheral blood mononuclear cells is the least sensitive method for detection of XMRV in subjects' blood.

Contamination of clinical specimens with MLV-encoding nucleic acids: implications for XMRV and other candidate human retroviruses

Reports from four independent research groups illustrate the extreme care needed to exclude DNA or RNA contamination in PCR analyses of XMRV, and phylogenetic evidence suggesting that previously-published XMRVs originated from a commonly-used prostate carcinoma cell line (22Rv1) is presented.

Spinal Fluid Abnormalities in Patients with Chronic Fatigue Syndrome

The results support two hypotheses: that some CFS patients have a neurological abnormality that may contribute to the clinical picture of the illness and that immune dysregulation within the central nervous system may be involved in this process.

Disease-associated XMRV sequences are consistent with laboratory contamination

It is proposed that Xenotropic murine leukaemia virus-related virus might not be a genuine human pathogen because of PCR contamination with mouse DNA and that the described clones of XMRV arose from the tumour cell line 22Rv1, which was probably infected with X MRV during xenografting in mice.