Biomedicine

Viruses in the Prostate

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Science  09 Feb 2007:
Vol. 315, Issue 5813, pp. 741
DOI: 10.1126/science.315.5813.741b

Twenty to 25% of human cancers are caused by viruses. The recognition that a virus plays an etiological role in a specific type cancer can profoundly change the ways in which that particular disease is diagnosed, treated, or prevented. One recent guidepost is cervical cancer, where the identification of human papillomavirus as a causal agent has led to the development of a promising prophylactic vaccine.

Previous studies have provided evidence in support of a possible viral origin for human prostate cancer. A retrovirus called XMRV (for xenotropic murine leukemia virus-related virus) was detected in 40% of prostate tumors from men who were homozygous for an allelic variant of the RNASEL gene and in only 2% of tumors from men of other genotypes. The RNASEL gene encodes RNase L, a ribonuclease whose activity is required for an innate antiviral response mediated by interferon (IFN); and, intriguingly, the allelic variant associated with XMRV-containing tumors encodes an enzyme with impaired activity.

Dong et al. show that a molecular viral clone of XMRV is infectious in human prostate cancer cell lines, that replication of the virus in vitro is sensitive to inhibition by IFN, and that suppression of RNase L enhances viral replication. In addition, they localized putative integration sites for the XMRV provirus to several host genes that encode functions with biologically plausible roles in prostate cancer, including a suppressor of androgen receptor transactivation. Still unanswered is the critical question of whether XMRV plays a causal role in prostate cancer, but these provocative observations should stimulate further experiments to sort this out. — PAK

Proc. Natl. Acad. Sci. U.S.A. 104, 1655 (2007).

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