4.6 Article

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

Journal

JOURNAL OF VIROLOGY
Volume 83, Issue 14, Pages 6995-7003

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00268-09

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Funding

  1. NCI/NIH [CA104943]
  2. U.S. Department of Defense Prostate Cancer Research Program [W81XWH-07-1-338]
  3. V Foundation for Cancer Research
  4. Prostate Cancer Foundation
  5. Charlotte Geyer Foundation
  6. Maltz Family Foundation
  7. Mal and Lea Bank Chair
  8. Wilhelm-Sander Foundation
  9. Deutsche Forschungsgemeinschaft

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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.

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