Laboratory of Retrovirology and Epigenetics, Center for AIDS Health Disparities Research, Vanderbilt-Meharry Center for AIDS Research (CFAR), Department of Biochemistry and Cancer Biology, 1050 Dr. D B Todd Jr. Blvd., Nashville TN 37208, TN, USA.
Virol J. 2011 Dec 12;8:531. doi: 10.1186/1743-422X-8-531.
Xenotropic murine leukemia virus (MLV)-related virus (XMRV) is a gammaretrovirus that was discovered in prostate cancer tissues. Recently, it has been proposed that XMRV is a laboratory contaminant and may have originated via a rare recombination event. Host restriction factor APOBEC3G (A3G) has been reported to severely restrict XMRV replication in human peripheral blood mononuclear cells. Interestingly, XMRV infects and replicates efficiently in prostate cancer cells of epithelial origin. It has been proposed that due to lack off or very low levels of A3G protein XMRV is able to productively replicate in these cells.
This report builds on and challenges the published data on the absence of A3G protein in prostate epithelial cells lines. We demonstrate the presence of A3G in prostate epithelial cell lines (LNCaP and DU145) by western blot and mass spectrometry. We believe the discrepancy in A3G detection is may be due to selection and sensitivity of A3G antibodies employed in the prior studies. Our results also indicate that XMRV produced from A3G expressing LNCaP cells can infect and replicate in target cells. Most importantly our data reveal downregulation of A3G in XMRV infected LNCaP and DU145 cells.
We propose that XMRV replicates efficiently in prostate epithelial cells by downregulating A3G expression. Given that XMRV lacks accessory proteins such as HIV-1 Vif that are known to counteract A3G function in human cells, our data suggest a novel mechanism by which retroviruses can counteract the antiviral effects of A3G proteins.
嗜性鼠白血病病毒（MLV）相关病毒（XMRV）是一种γ逆转录病毒，最初在前列腺癌组织中被发现。最近，有人提出 XMRV 是实验室污染物，可能是通过罕见的重组事件产生的。宿主限制因子 APOBEC3G（A3G）已被报道可严重限制人外周血单核细胞中的 XMRV 复制。有趣的是，XMRV 能够有效地感染和复制上皮来源的前列腺癌细胞。有人提出，由于缺乏或 A3G 蛋白水平非常低，XMRV 能够在这些细胞中进行有效复制。
本报告建立在先前关于前列腺上皮细胞系中缺乏 A3G 蛋白的发表数据的基础上，并对其进行了挑战。我们通过 Western blot 和质谱法证实了前列腺上皮细胞系（LNCaP 和 DU145）中存在 A3G。我们认为，在之前的研究中，A3G 检测的差异可能是由于所使用的 A3G 抗体的选择和敏感性不同。我们的结果还表明，来自表达 A3G 的 LNCaP 细胞产生的 XMRV 可以感染和复制靶细胞。最重要的是，我们的数据显示 XMRV 感染的 LNCaP 和 DU145 细胞中 A3G 的表达下调。
我们提出 XMRV 通过下调 A3G 表达在前列腺上皮细胞中高效复制。鉴于 XMRV 缺乏辅助蛋白，如已知可在人细胞中对抗 A3G 功能的 HIV-1 Vif，我们的数据表明了逆转录病毒对抗 A3G 蛋白的抗病毒作用的一种新机制。
