An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors Academic Article uri icon

Overview

MeSH Major

  • Interferons
  • Prostatic Neoplasms
  • Retroviridae

abstract

  • We recently reported identification of a previously undescribed gammaretrovirus genome, xenotropic murine leukemia virus-related virus (XMRV), in prostate cancer tissue from patients homozygous for a reduced activity variant of the antiviral enzyme RNase L. Here we constructed a full-length XMRV genome from prostate tissue RNA and showed that the molecular viral clone is replication-competent. XMRV replication in the prostate cancer cell line DU145 was sensitive to inhibition by IFN-beta. However, LNCaP prostate cancer cells, which are deficient in JAK1 and RNase L, were resistant to the effects of IFN-beta against XMRV. Furthermore, DU145 cells rendered deficient in RNase L with siRNA were partially resistant to IFN inhibition of XMRV. Expression in hamster cells of the xenotropic and polytropic retrovirus receptor 1 allowed these cells to be infected by XMRV. XMRV provirus integration sites were mapped in DNA isolated from human prostate tumor tissue to genes for two transcription factors (NFATc3 and CREB5) and to a gene encoding a suppressor of androgen receptor transactivation (APPBP2/PAT1/ARA67). Our studies demonstrate that XMRV is a virus that has infected humans and is susceptible to inhibition by IFN and its downstream effector, RNase L.

publication date

  • January 30, 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1776164

Digital Object Identifier (DOI)

  • 10.1073/pnas.0610291104

PubMed ID

  • 17234809

Additional Document Info

start page

  • 1655

end page

  • 60

volume

  • 104

number

  • 5