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Journal of Virology, July 2009, p. 6995-7003, Vol. 83, No. 14
0022-538X/09/$08.00+0     doi:10.1128/JVI.00268-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Fibrils of Prostatic Acid Phosphatase Fragments Boost Infections with XMRV (Xenotropic Murine Leukemia Virus-Related Virus), a Human Retrovirus Associated with Prostate Cancer{triangledown}

Seunghee Hong,1,2 Eric A. Klein,3 Jaydip Das Gupta,1 Kirsten Hanke,4 Christopher J. Weight,3 Carvell Nguyen,3 Christina Gaughan,1 Kyeong-Ae Kim,5 Norbert Bannert,4 Frank Kirchhoff,5 Jan Munch,5 and Robert H. Silverman1,3*

Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195,1 Graduate Program in Molecular Virology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106,2 Glickman Urological and Kidney Institute and Taussig Cancer Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195,3 Robert Koch-Institute, Centre for Biological Safety 4, Nordufer 20, 13353 Berlin, Germany,4 Institute of Virology, University Clinic of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany5

Received 6 February 2009/ Accepted 21 April 2009

The xenotropic murine leukemia virus-related virus (XMRV) has recently been detected in prostate cancer tissues and may play a role in tumorigenesis. It is currently unclear how this virus is transmitted and which factors promote its spread in the prostate. We show that amyloidogenic fragments known as semen-derived enhancer of virus infection (SEVI) originating from prostatic acid phosphatase greatly increase XMRV infections of primary prostatic epithelial and stromal cells. Hybrid simian/human immunodeficiency chimeric virus particles pseudotyped with XMRV envelope protein were used to demonstrate that the enhancing effect of SEVI, or of human semen itself, was at the level of viral attachment and entry. SEVI enhanced XMRV infectivity but did not bypass the requirement for the xenotropic and polytropic retrovirus receptor 1. Furthermore, XMRV RNA was detected in prostatic secretions of some men with prostate cancer. The fact that the precursor of SEVI is produced in abundance by the prostate indicates that XMRV replication occurs in an environment that provides a natural enhancer of viral infection, and this may play a role in the spread of this virus in the human population.

* Corresponding author. Mailing address: Cleveland Clinic, 9500 Euclid Avenue NB40, Cleveland, OH 44195. Phone: (216) 445-9650. Fax: (216) 445-6269. E-mail: silverr{at}ccf.org

{triangledown} Published ahead of print on 29 April 2009.

Journal of Virology, July 2009, p. 6995-7003, Vol. 83, No. 14
0022-538X/09/$08.00+0     doi:10.1128/JVI.00268-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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