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The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome

Nature Reviews Urology volume 7, pages 392–402 (2010)Cite this article

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Abstract

Xenotropic murine leukemia virus-related virus (XMRV) is an authentic, newly recognized human retrovirus first identified in prostate cancer tissues from men with a deficiency in the innate immunity gene RNASEL. At present, studies have detected XMRV at widely different rates in prostate cancer cases (0–27%) and in patients with chronic fatigue syndrome (CFS; 0–67%). Indirect or direct modes of carcinogenesis by XMRV have been suggested depending on whether the virus was found in stroma or malignant epithelium. Viral replication in the prostate might be affected by androgens, which stimulate XMRV through a transcriptional enhancer site in viral DNA. By contrast, host restriction factors, such as APOBEC3 and tetherin, inhibit virus replication. Immune dysfunction mediated by XMRV has been suggested as a possible factor in CFS. Recent studies show that some existing antiretroviral drugs suppress XMRV infections and diagnostic assays are under development. 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. Emerging science surrounding XMRV is contributing to our knowledge of retroviral infections while focusing intense interest on two major human diseases.

Key Points

  • Infection, inflammation and genetics are all risk factors in prostate cancer development

  • Xenotropic murine leukemia virus-related virus (XMRV) is a newly discovered retrovirus identified in some, but not all, studies of prostate cancer and chronic fatigue syndrome

  • A viral etiology is suspected but not proven for either disease

  • XMRV oncogenesis by insertional activation of host genes followed by androgen stimulation might lead to chronic inflammation and cell transformation in the prostate

  • XMRV could present opportunities for diagnosis, treatment and prevention of these diseases via development of biomarkers, antiretroviral therapies, and vaccines, respectively

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Figure 1: Phylogeny of nucleotide sequences of XMRV with other gammaretroviruses.
Figure 2: Structure of xenotropic murine leukemia virus-related virus.
Figure 3: Potential role of XMRV in prostate cancer and CFS.

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Acknowledgements

We wish to gratefully acknowledge financial support for our research studies from the NIH (NCI), grant CA103943, US Department of Defense, grant W81XWH-07-1-338, Mal and Lea Bank, the Charlotte Geyer Foundation, the Milton and Tamar Maltz Family Foundation, and Abbott Laboratories.

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  1. Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, 44195, OH, USA

    Robert H. Silverman

  2. Glickman Urologic and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, 44195, OH, USA

    Carvell Nguyen, Christopher J. Weight & Eric A. Klein

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Correspondence to Robert H. Silverman.

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All authors hold patents, or have patent applications pending, with Abbott Laboratories. In addition, Robert H. Silverman has been a consultant for, and received grant/research support from, Abbott Laboratories.

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Silverman, R., Nguyen, C., Weight, C. et al. The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome. Nat Rev Urol 7, 392–402 (2010). https://doi.org/10.1038/nrurol.2010.77

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