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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
BACKGROUND: In 2009, a retrospective study reported the detection of xenotropic murine leukemia virus-related virus (XMRV) in clinical isolates derived from individuals with chronic fatigue syndrome or myalgic encephalomyelitis (CFS). While many efforts to confirm this observation failed, one report...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236736/ https://www.ncbi.nlm.nih.gov/pubmed/25092471 http://dx.doi.org/10.1186/1756-0500-7-461 |
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author | Irlbeck, David M Vernon, Suzanne D McCleary, K Kimberly Bateman, Lucinda Klimas, Nancy G Lapp, Charles W Peterson, Daniel L Brown, James R Remlinger, Katja S Wilfret, David A Gerondelis, Peter |
author_facet | Irlbeck, David M Vernon, Suzanne D McCleary, K Kimberly Bateman, Lucinda Klimas, Nancy G Lapp, Charles W Peterson, Daniel L Brown, James R Remlinger, Katja S Wilfret, David A Gerondelis, Peter |
author_sort | Irlbeck, David M |
collection | PubMed |
description | BACKGROUND: In 2009, a retrospective study reported the detection of xenotropic murine leukemia virus-related virus (XMRV) in clinical isolates derived from individuals with chronic fatigue syndrome or myalgic encephalomyelitis (CFS). While many efforts to confirm this observation failed, one report detected polytropic murine leukemia virus (pMLV), instead of XMRV. In both studies, Polymerase Chain Reaction (PCR)-based methods were employed which could provide the basis for the development of a practical diagnostic tool. To confirm these studies, we hypothesized that the ability to detect these viruses will not only depend upon the technical details of the methods employed but also on the criteria used to diagnose CFS and the availability of well characterized clinical isolates. METHODS: A repository of clinical isolates from geographically distinct sites was generated by the collection of fresh blood samples from well characterized CFS and healthy subjects. Molecular techniques were used to generate assay positive controls and to determine the lower limit of detection (LLOD) for murine retroviral and Intracisternal A particle (Cell 12(4):963-72, 1977) detection methods. RESULTS: We report the establishment of 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 isolates from individuals with CFS in a blinded, multi-site, prospective study. We detected various, murine retroviral DNA signatures but were unable to resolve a difference in the incidence of their detection between isolates from CFS (5/72; 6.7%) and healthy (2/37; 5.4%) subjects (Fisher’s Exact Test, p-value = 1). The observed sequences appeared to reflect the detection of endogenous murine retroviral DNA, which was not identical to either XMRV or pMLV. CONCLUSIONS: We were unable to confirm a previously reported association between the detection of XMRV or pMLV sequences and CFS in a prospective, multi-site study. Murine retroviral sequences were detected at a low frequency that did not differ between CFS and control subjects. The nature of these sequences appeared to reflect the detection of pre-existing, endogenous, murine retroviral DNA in the PCR reagents employed. |
format | Online Article Text |
id | pubmed-4236736 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42367362014-11-20 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 Irlbeck, David M Vernon, Suzanne D McCleary, K Kimberly Bateman, Lucinda Klimas, Nancy G Lapp, Charles W Peterson, Daniel L Brown, James R Remlinger, Katja S Wilfret, David A Gerondelis, Peter BMC Res Notes Research Article BACKGROUND: In 2009, a retrospective study reported the detection of xenotropic murine leukemia virus-related virus (XMRV) in clinical isolates derived from individuals with chronic fatigue syndrome or myalgic encephalomyelitis (CFS). While many efforts to confirm this observation failed, one report detected polytropic murine leukemia virus (pMLV), instead of XMRV. In both studies, Polymerase Chain Reaction (PCR)-based methods were employed which could provide the basis for the development of a practical diagnostic tool. To confirm these studies, we hypothesized that the ability to detect these viruses will not only depend upon the technical details of the methods employed but also on the criteria used to diagnose CFS and the availability of well characterized clinical isolates. METHODS: A repository of clinical isolates from geographically distinct sites was generated by the collection of fresh blood samples from well characterized CFS and healthy subjects. Molecular techniques were used to generate assay positive controls and to determine the lower limit of detection (LLOD) for murine retroviral and Intracisternal A particle (Cell 12(4):963-72, 1977) detection methods. RESULTS: We report the establishment of 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 isolates from individuals with CFS in a blinded, multi-site, prospective study. We detected various, murine retroviral DNA signatures but were unable to resolve a difference in the incidence of their detection between isolates from CFS (5/72; 6.7%) and healthy (2/37; 5.4%) subjects (Fisher’s Exact Test, p-value = 1). The observed sequences appeared to reflect the detection of endogenous murine retroviral DNA, which was not identical to either XMRV or pMLV. CONCLUSIONS: We were unable to confirm a previously reported association between the detection of XMRV or pMLV sequences and CFS in a prospective, multi-site study. Murine retroviral sequences were detected at a low frequency that did not differ between CFS and control subjects. The nature of these sequences appeared to reflect the detection of pre-existing, endogenous, murine retroviral DNA in the PCR reagents employed. BioMed Central 2014-08-04 /pmc/articles/PMC4236736/ /pubmed/25092471 http://dx.doi.org/10.1186/1756-0500-7-461 Text en Copyright © 2014 Irlbeck et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Irlbeck, David M Vernon, Suzanne D McCleary, K Kimberly Bateman, Lucinda Klimas, Nancy G Lapp, Charles W Peterson, Daniel L Brown, James R Remlinger, Katja S Wilfret, David A Gerondelis, Peter 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236736/ https://www.ncbi.nlm.nih.gov/pubmed/25092471 http://dx.doi.org/10.1186/1756-0500-7-461 |
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