Xenotropic Murine Leukemia Virus-Related Virus Establishes an Efficient Spreading Infection and Exhibits Enhanced Transcriptional Activity in Prostate Carcinoma Cells
Xenotropic Murine Leukemia Virus-Related Virus Establishes an Efficient Spreading Infection and Exhibits Enhanced Transcriptional Activity in Prostate Carcinoma Cells
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DOI：
10.1128/jvi.01969-09
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发表时间：
2010-03-01
影响因子：
5.4
通讯作者：
Goff, Stephen P.
中科院分区：
文献类型：
--
作者：
Rodriguez, Jason J.;Goff, Stephen P.
异嗜性小鼠白血病病毒相关病毒（XMRV）是一种与人前列腺肿瘤相关的新型人γ -逆转录病毒。XMRV首先在携带HPC1基因位点突变的患者肿瘤周围的前列腺基质细胞中被发现。为了确定XMRV在细胞培养中的趋向性，我们测试了XMRV在各种前列腺和非前列腺细胞系中传播和复制的能力。我们发现，尽管XMRV病毒蛋白的表达和感染病毒的传播在多种细胞系中都是最小的，但XMRV在LNCaP前列腺肿瘤细胞中表现出强劲的表达和感染。在LNCaP和wpmy1（猿猴病毒40-转化前列腺基质细胞）中，XMRV长末端重复序列（LTR）的转录活性均高于Moloney小鼠白血病病毒LTR。在LNCaP细胞中，XMRV的U3启动子和U3中的糖皮质激素反应元件（GRE）是转录活性所必需的。雄激素受体的共表达和双氢睾酮的刺激刺激了293T细胞中xmrv - ltr依赖的转录，而这种活性需要GRE。这些数据表明，XMRV可能在LNCaP细胞中更有效地复制，部分原因是LNCaP细胞中的转录环境。
Xenotropic murine leukemia virus-related virus (XMRV) is a novel human gammaretrovirus discovered in association with human prostate tumors. XMRV was first identified in prostate stromal cells surrounding the tumors of patients carrying a mutation in the HPC1 gene locus. To determine the tropism of XMRV in cell culture, we tested the ability of XMRV to spread and replicate in various prostate and nonprostate cell lines. We found that although the expression of XMRV viral proteins and the spread of infectious virus were minimal in a variety of cell lines, XMRV displayed robust expression and infection in LNCaP prostate tumor cells. The transcriptional activity of the XMRV long terminal repeat (LTR) was found to be higher than the Moloney murine leukemia virus LTRs in both LNCaP and WPMY-1 (simian virus 40-transformed prostate stromal cells). The U3 promoter of XMRV and a glucocorticoid response element (GRE) within the U3 were required for the transcriptional activity in LNCaP cells. Coexpression of the androgen receptor and stimulation with dihydrotestosterone stimulated XMRV-LTR-dependent transcription in 293T cells, and the GRE was required for this activity. These data suggest that XMRV may replicate more efficiently in LNCaP cells in part due to the transcriptional environment in LNCaP cells.