Journal Article

The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome

Silverman, Robert H., Weight, Christopher J., Klein, Eric A., Nguyen, Carvell

2010

Overview

Identification of xenotropic murine leukemia virus-related virus (XMRV) in patients with prostate cancer or chronic fatigue syndrome has spurred a flurry of research activity. Different research groups have had dramatically disparate results. In this Review, Robert Silverman and colleagues address the many questions, issues and controversies that require resolution. 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

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/326/596/1787 / 631/67/1858 / 631/80/304 / 692/699/67/589/466 / Anti-Retroviral Agents - pharmacology / Anti-Retroviral Agents - therapeutic use / Biology / Care and treatment / Chronic fatigue syndrome / Diagnosis / Fatigue Syndrome, Chronic - immunology / Fatigue Syndrome, Chronic - therapy / Fatigue Syndrome, Chronic - virology / Female / Gammaretrovirus - drug effects / Gammaretrovirus - immunology / Gammaretrovirus - pathogenicity / Genes / Genetic aspects / Health aspects / Humans / Infections / Inflammation / Leukemia / Leukemia Virus, Murine - drug effects / Leukemia Virus, Murine - immunology / Leukemia Virus, Murine - pathogenicity / Male / Medicine / Medicine & Public Health / Mouse leukemia viruses / Prostate cancer / Prostatic Neoplasms - immunology / Prostatic Neoplasms - therapy / Prostatic Neoplasms - virology / Retroviridae - drug effects / Retroviridae - immunology / Retroviridae - pathogenicity / Retroviridae Infections - immunology / Retroviridae Infections - therapy / Retroviridae Infections - virology / review-article / Risk factors / Sexually transmitted diseases / STD / Tumor Virus Infections - immunology / Tumor Virus Infections - therapy / Tumor Virus Infections - virology / Urology / Viral infections / Viruses