Work on novel virus in prostate cancer makes the cover of PNAS and is highlighted by Science.

Recent work from Dr. Robert Silverman's lab was published in PNAS (Dong, B. et al, "An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors," PNAS 2007 104: 1655) and highlighted on its cover and in a commentary (Fan, H., "A new human retrovirus associated with prostate cancer," PNAS 2007 104: 1449.) In addition, the report was selected by the Editor of Science as the most important paper of the week in the Biomedicine category.

The commentary from Science follows:

Volume 315, Number 5813, Issue of 09 February 2007
©2007 by The American Association for the Advancement of Science.

BIOMEDICINE: Viruses in the Prostate

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