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.
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Authors | Beihua Dong, Sanggu Kim, Seunghee Hong, Jaydip Das Gupta, Krishnamurthy Malathi, Eric A Klein, Don Ganem, Joseph L Derisi, Samson A Chow, Robert H Silverman |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 104
Issue 5
Pg. 1655-60
(Jan 30 2007)
ISSN: 0027-8424 [Print] United States |
PMID | 17234809
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- RNA, Small Interfering
- Interferons
- Janus Kinase 1
- Endoribonucleases
- 2-5A-dependent ribonuclease
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Topics |
- Animals
- CHO Cells
- Cell Line, Tumor
- Cricetinae
- Cricetulus
- Endoribonucleases
(metabolism)
- Humans
- Interferons
(metabolism)
- Janus Kinase 1
(metabolism)
- Male
- Molecular Sequence Data
- Open Reading Frames
- Prostatic Neoplasms
(genetics)
- RNA, Small Interfering
(metabolism)
- Retroviridae
(metabolism)
- Transcriptional Activation
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