Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Disease-associated XMRV sequences are consistent with laboratory contamination
Retrovirology, Volume 7, Article 111, Year 2010
Notification
URL copied to clipboard!
Description
Background: Xenotropic murine leukaemia viruses (MLV-X) are endogenous gammaretroviruses that infect cells from many species, including humans. Xenotropic murine leukaemia virus-related virus (XMRV) is a retrovirus that has been the subject of intense debate since its detection in samples from humans with prostate cancer (PC) and chronic fatigue syndrome (CFS). Controversy has arisen from the failure of some studies to detect XMRV in PC or CFS patients and from inconsistent detection of XMRV in healthy controls.Results: Here we demonstrate that Taqman PCR primers previously described as XMRV-specific can amplify common murine endogenous viral sequences from mouse suggesting that mouse DNA can contaminate patient samples and confound specific XMRV detection. To consider the provenance of XMRV we sequenced XMRV from the cell line 22Rv1, which is infected with an MLV-X that is indistinguishable from patient derived XMRV. Bayesian phylogenies clearly show that XMRV sequences reportedly derived from unlinked patients form a monophyletic clade with interspersed 22Rv1 clones (posterior probability >0.99). The cell line-derived sequences are ancestral to the patient-derived sequences (posterior probability >0.99). Furthermore, pol sequences apparently amplified from PC patient material (VP29 and VP184) are recombinants of XMRV and Moloney MLV (MoMLV) a virus with an envelope that lacks tropism for human cells. Considering the diversity of XMRV we show that the mean pairwise genetic distance among env and pol 22Rv1-derived sequences exceeds that of patient-associated sequences (Wilcoxon rank sum test: p = 0.005 and p < 0.001 for pol and env, respectively). Thus XMRV sequences acquire diversity in a cell line but not in patient samples. These observations are difficult to reconcile with the hypothesis that published XMRV sequences are related by a process of infectious transmission.Conclusions: We provide several independent lines of evidence that XMRV detected by sensitive PCR methods in patient samples is the likely result 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 XMRV during xenografting in mice. We propose that XMRV might not be a genuine human pathogen. © 2010 Hué et al; licensee BioMed Central Ltd.
Authors & Co-Authors
Hué, Stéphane
United Kingdom, London
Medical Research Council
Gray, Eleanor R.
United Kingdom, London
Medical Research Council
Gall, Astrid
United Kingdom, Hinxton
Wellcome Sanger Institute
Katzourakis, Aris I.
United Kingdom, Oxford
University of Oxford
Houldcroft, Charlotte J.
United Kingdom, Hinxton
Wellcome Sanger Institute
Morris, Lynn G.
United Kingdom, London
Medical Research Council
Futreal, Phillip Andrew
United Kingdom, Hinxton
Wellcome Sanger Institute
Garson, Jeremy A.
United Kingdom, London
Medical Research Council
Pybus, Oliver George
United Kingdom, Oxford
University of Oxford
Kellam, P.
United Kingdom, London
Medical Research Council
United Kingdom, Hinxton
Wellcome Sanger Institute
Towers, Greg J.
United Kingdom, London
Medical Research Council
Statistics
Citations: 155
Authors: 11
Affiliations: 3
Identifiers
Doi:
10.1186/1742-4690-7-111
ISSN:
17424690
Research Areas
Cancer
Genetics And Genomics
Health System And Policy