New Insight Gained Into Virus Linked with Prostate Cancer

Robert Silverman, PhD In 2006, Cleveland Clinic researchers, together with investigators at the University of California at San Francisco, made the landmark discovery of a human virus that appears to be associated with prostate cancer. Since then, however, it's been unclear how the virus is transmitted and which factors promote its spread in the prostate.

But the inner workings of the virus called xenotropic murine leukemia virus-related virus (XMRV) are becoming more in focus.

Seunghee Hong, a graduate student at Case Western Reserve University in Cleveland, Robert Silverman, PhD, of the Institute's Department of Cancer Biology, and Eric Klein, MD, Chair of the Cleveland Clinic Glickman Urological and Kidney Institute, now report that XMRV may be promulgated in a manner similar to that of sexually transmitted diseases (STDs).

The team discovered that fine threads of a substance called semen-derived enhancer of virus infection (SEVI) enhance the ability of XMRV to infect the prostate. SEVI consists of amyloid fibrils of prostatic acid phosphatase fragments, an enzyme that is abundant in semen.

In what may be a mode similar to that found with HIV infection, this enhancement may involve promoting virus interaction or even fusion with target cells.

Semen causes increases in the ability of XMRV to infect, in part because it contains SEVI. Prior studies by Dr. Silverman have shown that XMRV is associated with a variant of the RNase L gene. But it now appears that additional host factors also may be involved.

Drs. Silverman and Klein found that XMRV duplicates at a 10-fold higher level in the epithelial cells that form the glandular portion of the prostate from which prostate cancer arises than in the stromal cells that form the gland's supporting framework.

Epidemiologic studies suggest that men with a history of sexually transmitted infections may carry a higher risk of prostate cancer. Because SEVI and semen lower the threshold of viral infection in many cell types in the genitourinary tract, the investigators think XMRV may be a type of sexually transmitted infection and that SEVI may be critical for the spread of XMRV in the human prostate and hence possibly in prostate cancer.

It's still unknown if XMRV is a passenger virus or a causative factor. "But if we can establish this virus as a cofactor of prostate cancer, detection of XMRV could provide an early indicator of prostate cancer development or disease aggressiveness in some patients. There could be strategies that one could take to block the virus, such as antiviral agents or vaccines," Dr. Silverman said.

Drs. Silverman and Klein published with coworkers Seunghee Hong, Jaydip Das Gupta, and Christina Gaughan, of the Institute's Department of Cancer Biology; Carvell Nguyen, MD, and Christopher J. Weight, MD, both of the Glickman Institute; Kirsten Hanke and Norbert Bannert, Robert Koch-Institute's Centre for Biological Safety, Berlin, Germany; and Kyeong-Ae Kim, Frank Kirchhoff, and Jan Munch, University Clinic of Ulm's Institute of Virology, Ulm, Germany. The findings appeared in the Journal of Virology (http://jvi.asm.org/, 2009 Jul;83:6995-7003).