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Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration
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Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration

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An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors

Beihua Dong1, Sanggu Kim, Seunghee Hong

  • 1Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 20, 2007
PubMed

Insights

Xenotropic murine leukemia virus-related virus (XMRV) infects human prostate cancer cells and is inhibited by interferon-beta (IFN-beta) and RNase L. This study confirms XMRV is a human-infecting gammaretrovirus susceptible to antiviral defenses.

Area of Science:

  • Virology
  • Oncology
  • Immunology

Background:

  • Xenotropic murine leukemia virus-related virus (XMRV), a gammaretrovirus, was identified in prostate cancer tissues.
  • Patients with XMRV harbored a variant of the antiviral enzyme RNase L with reduced activity.

Purpose of the Study:

  • To construct a full-length XMRV genome and assess its replication competence.
  • To investigate the susceptibility of XMRV to interferon-beta (IFN-beta) and RNase L.
  • To identify XMRV provirus integration sites in human prostate tumor DNA.

Main Methods:

  • Full-length XMRV genome construction from prostate tissue RNA.
  • Replication competence assay in DU145 and LNCaP prostate cancer cell lines.
  • IFN-beta inhibition assays in cells with varying RNase L and JAK1 expression.
  • Xenotropic and polytropic retrovirus receptor 1 expression in hamster cells for infection studies.
  • Provirus integration site mapping using DNA from human prostate tumor tissue.

Main Results:

  • A replication-competent XMRV molecular clone was successfully constructed.
  • XMRV replication was sensitive to IFN-beta in DU145 cells but resistant in RNase L-deficient LNCaP cells.
  • RNase L deficiency partially conferred resistance to IFN-beta inhibition of XMRV.
  • Hamster cells expressing the XMRV receptor were susceptible to infection.
  • XMRV provirus integrated into genes encoding transcription factors (NFATc3, CREB5) and an androgen receptor suppressor (APPBP2/PAT1/ARA67).

Conclusions:

  • XMRV is a human-infecting virus.
  • XMRV replication is susceptible to inhibition by IFN and its downstream effector, RNase L.
  • Understanding XMRV's interaction with host antiviral mechanisms is crucial for therapeutic strategies.

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