Disease-associated XMRV sequences are consistent with laboratory contamination
<p>Abstract</p> <p>Background</p> <p>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 i...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-12-01
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| Series: | Retrovirology |
| Online Access: | http://www.retrovirology.com/content/7/1/111 |
| _version_ | 1818111596345425920 |
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| author | Garson Jeremy A Futreal Andrew Pillay Deenan McLaren Stuart Houldcroft Charlotte J Tan Choon Katzourakis Aris Gall Astrid Gray Eleanor R Hué Stéphane Pybus Oliver G Kellam Paul Towers Greg J |
| author_facet | Garson Jeremy A Futreal Andrew Pillay Deenan McLaren Stuart Houldcroft Charlotte J Tan Choon Katzourakis Aris Gall Astrid Gray Eleanor R Hué Stéphane Pybus Oliver G Kellam Paul Towers Greg J |
| author_sort | Garson Jeremy A |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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, <it>pol </it>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 <it>env </it>and <it>pol </it>22Rv1-derived sequences exceeds that of patient-associated sequences (Wilcoxon rank sum test: p = 0.005 and p < 0.001 for <it>pol </it>and <it>env</it>, 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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-11T03:05:33Z |
| format | Article |
| id | doaj.art-b5d73955168843098b53717154371dea |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-11T03:05:33Z |
| publishDate | 2010-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-b5d73955168843098b53717154371dea2022-12-22T01:22:58ZengBMCRetrovirology1742-46902010-12-017111110.1186/1742-4690-7-111Disease-associated XMRV sequences are consistent with laboratory contaminationGarson Jeremy AFutreal AndrewPillay DeenanMcLaren StuartHouldcroft Charlotte JTan ChoonKatzourakis ArisGall AstridGray Eleanor RHué StéphanePybus Oliver GKellam PaulTowers Greg J<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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, <it>pol </it>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 <it>env </it>and <it>pol </it>22Rv1-derived sequences exceeds that of patient-associated sequences (Wilcoxon rank sum test: p = 0.005 and p < 0.001 for <it>pol </it>and <it>env</it>, 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.</p> <p>Conclusions</p> <p>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.</p>http://www.retrovirology.com/content/7/1/111 |
| spellingShingle | Garson Jeremy A Futreal Andrew Pillay Deenan McLaren Stuart Houldcroft Charlotte J Tan Choon Katzourakis Aris Gall Astrid Gray Eleanor R Hué Stéphane Pybus Oliver G Kellam Paul Towers Greg J Disease-associated XMRV sequences are consistent with laboratory contamination Retrovirology |
| title | Disease-associated XMRV sequences are consistent with laboratory contamination |
| title_full | Disease-associated XMRV sequences are consistent with laboratory contamination |
| title_fullStr | Disease-associated XMRV sequences are consistent with laboratory contamination |
| title_full_unstemmed | Disease-associated XMRV sequences are consistent with laboratory contamination |
| title_short | Disease-associated XMRV sequences are consistent with laboratory contamination |
| title_sort | disease associated xmrv sequences are consistent with laboratory contamination |
| url | http://www.retrovirology.com/content/7/1/111 |
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