XMRV, prostate cancer, and chronic fatigue syndrome

Robert H. Silverman, one of the authors on the study implicating the new human retrovirus XMRV as an etiologic agent of chronic fatigue syndrome, has written an excellent review article on the current status of research on the virus. The article is behind a paywall at Nature Reviews Urology, so I’ll provide a summary of the salient points.

The article begins with a description of how XMRV DNA was isolated from surgically removed prostate tumor tissue. Sequence analysis of three strains showed that the virus is most closely related to xenotropic and polytropic murine leukemia viruses and hence was named xenotropic murine leukemia virus-related virus, or XMRV. Five lines of evidence indicate that XMRV is not a laboratory contaminant:

  • XMRV was detected in RNA isolated from human prostate tissue
  • Mouse sequences were not detected in the human prostate tissues
  • Infections were mainly found in tissues from humans with an alteration in the protein RNAse L
  • Slightly different viral sequences (polymorphisms) were identified in isolates from different patients
  • Both viral RNA and viral proteins were detected in prostate tissues

The article continues with a summary of  subsequent studies in which XMRV has or has not been detected in prostate cancer, then moves to the role of XMRV in CFS. Silverman concludes that “the scientific literature shows that XMRV was detected in the majority, but not all, prostate cancer studies, albeit at different rates, while XMRV was found in CFS in only one study of four published to date.” He offers the the following explanations for the difference in detection of XMRV in prostate cancer and CFS:

  • Viral contamination from mouse sources. This cannot explain all positive findings in different laboratories using different experimental techniques.
  • Geographical differences in the distribution of XMRV could account for some of the differences.
  • Sequence differences could lead to failure to detect viral DNA by polymerase chain reaction.
  • There are no standardized, sensitive methods of detection, and no widely available positive control samples.

The remainder of the article entails speculation on how XMRV might cause prostate cancer; the likely origin of the virus from a rodent virus; and antiviral drugs that are known to inhibit replication of the virus. It ends with the suggestion to test for the presence of XMRV in porcine tissues used for human transplantation, and in the blood supply, to avoid additional infections.

Silverman concludes:

Although other retroviruses of the same genus as XMRV (gammaretroviruses) cause cancer and neurological disease in animals, whether XMRV is a cause of either prostate cancer or CFS remains unknown.

Robert H. Silverman, Carvell Nguyen, Christopher J. Weight & Eric A. Klein. The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome. Nature Reviews Urology doi: 10.1038/nrurol.2010.77.

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