XMRV and Public Health: The Retroviral Genome Is Not a Suitable Template for Diagnostic PCR

AndyPR

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XMRV and Public Health: The Retroviral Genome Is Not a Suitable Template for Diagnostic PCR, and Its Association with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Appears Unreliable.

Panelli S1,2, Lorusso L3, Balestrieri A4, Lupo G1,2, Capelli E1,2.
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Abstract

A few years ago, a highly significant association between the xenotropic murine leukemia virus-related virus (XMRV) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a complex debilitating disease of poorly understood etiology and no definite treatment, was reported in Science, raising concern for public welfare. Successively, the failure to reproduce these findings, and the suspect that the diagnostic PCR was vitiated by laboratory contaminations, led to the retraction of the paper. Notwithstanding, XMRV continued to be the subject of researches and public debates. Occasional positivity in humans was also detected recently, even if the data always appeared elusive and non-reproducible.

In this study, we discuss the current status of this controversial association and propose that a major role in the unreliability of the results was played by the XMRV genomic composition in itself. In this regard, we present bioinformatic analyses that show: (i) aspecific, spurious annealings of the available primers in multiple homologous sites of the human genome; (ii) strict homologies between whole XMRV genome and interspersed repetitive elements widespread in mammalian genomes.

To further detail this scenario, we screen several human and mammalian samples by using both published and newly designed primers. The experimental data confirm that available primers are far from being selective and specific.

In conclusion, the occurrence of highly conserved, repeated DNA sequences in the XMRV genome deeply undermines the reliability of diagnostic PCRs by leading to artifactual and spurious amplifications. Together with all the other evidences, this makes the association between the XMRV retrovirus and CFS totally unreliable.
https://www.ncbi.nlm.nih.gov/pubmed/28589117

Open access PDF - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439170/pdf/fpubh-05-00108.pdf
And online version - http://journal.frontiersin.org/article/10.3389/fpubh.2017.00108/full
 

Esther12

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In some ways I'm surprised that papers are still being published on this. Maybe it took them a long time to write up and get published?
 

AndyPR

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In some ways I'm surprised that papers are still being published on this. Maybe it took them a long time to write up and get published?
I just spotted it being linked elsewhere so have no extra info unfortunately, other than what is on the paper itself.
Received:
15 November 2016
Accepted:
02 May 2017
Published:
22 May 2017
 

Valentijn

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In some ways I'm surprised that papers are still being published on this. Maybe it took them a long time to write up and get published?
This seems to be more about the genetic aspect of XMRV, though the ME/CFS controversy is what presented them with an interesting puzzle. From what I can understand after a quick skim, PCR techniques present a problem here because segments of the host's own DNA (possibly of ancient retroviral origins) can end up looking very similar to the sequences used to identify XMRV.