An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors
An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors
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DOI：
10.1073/pnas.0610291104
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发表时间：
2007-01-30
影响因子：
11.1
通讯作者：
Silverman, Robert H.
中科院分区：
文献类型：
--
作者：
Dong, Beihua;Kim, Sanggu;Silverman, Robert H.
我们最近报道在前列腺癌组织中发现了一种以前未被描述的伽玛逆转录病毒基因组，异嗜性小鼠白血病病毒相关病毒(XMRV)，该病毒是从抗病毒酶RNaseL活性降低的纯合子患者的前列腺癌组织中检测到的。在这里，我们从前列腺组织RNA中构建了全长XMRV基因组，并证明了该分子病毒克隆具有复制能力。XMRV在前列腺癌DU145细胞中的复制对IFIN-β的抑制很敏感。然而，缺乏JAK1和核糖核酸酶L的LNCaP前列腺癌细胞对IFIN-β对XMRV的作用具有抵抗力。此外，核糖核酸酶L基因缺失的DU145细胞对干扰素抑制XMRV有部分抗性。异嗜性和多嗜性逆转录病毒受体1在仓鼠细胞中的表达使这些细胞能够被XMRV感染。从人前列腺癌组织中分离的XMRV前病毒整合位点被定位到两个转录因子(NFATc3和CREB5)的基因和一个编码雄激素受体反式激活抑制因子的基因(APPBP2/PAT1/ARA67)。我们的研究表明，XMRV是一种感染人类的病毒，对干扰素及其下游效应物RNaseL敏感。
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 IFIN-beta. However, LNCaP prostate cancer cells, which are deficient in JAK1 and RNase L, were resistant to the effects of IFIN-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.