Apobec 3G efficiently reduces infectivity of the human exogenous gammaretrovirus XMRV.
Apobec 3G efficiently reduces infectivity of the human exogenous gammaretrovirus XMRV.
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DOI：
10.1371/journal.pone.0011738
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发表时间：
2010-07-23
期刊：
影响因子：
3.7
通讯作者：
Fischer N
中科院分区：
文献类型：
--
作者：
Stieler K;Fischer N
人外源性伽玛病毒XMRV被认为与前列腺癌和慢性疲劳综合征有关。除了紧迫的流行病学问题外，阐明该病毒的组织和细胞趋向性及其对逆转录病毒限制因子的敏感性也具有重要意义。Apobec3 （A3）蛋白是胞苷脱氨酶的一个家族，是控制原发感染和有效病毒传播的一组重要宿主蛋白。在这里，我们证明了XMRV对人类Apobec 3B， 3C和3F具有耐药性，同时对人类A3G蛋白高度敏感，这是一种已知对大多数逆转录病毒具有抗病毒活性的因子。我们发现XMRV和MoMLV病毒粒子独立于它们的特异性限制性活性包装载脂蛋白。hA3G被发现是XMRV和MoMLV感染性的有效抑制剂。与MoMLV相比，XMRV感染也可以通过低浓度的mA3部分减少。有趣的是，已建立的对XMRV感染高度敏感的前列腺癌细胞系不或仅弱表达hA3G。我们的研究结果证实并扩展了最近发表的数据，表明hA3G限制XMRV感染。该结果将对探索哪些细胞被XMRV感染并有效支持病毒在体内传播具有价值。此外，观察到mA3可以减少XMRV感染，这与目前XMRV感染的自然库有关。
The human exogenous gammaretrovirus XMRV is thought to be implicated in prostate cancer and chronic fatigue syndrome. Besides pressing epidemiologic questions, the elucidation of the tissue and cell tropism of the virus, as well as its sensitivity to retroviral restriction factors is of fundamental importance. The Apobec3 (A3) proteins, a family of cytidine deaminases, are one important group of host proteins that control primary infection and efficient viral spread. Here we demonstrate that XMRV is resistant to human Apobec 3B, 3C and 3F, while being highly susceptible to the human A3G protein, a factor which is known to confer antiviral activity against most retroviruses. We show that XMRV as well as MoMLV virions package Apobec proteins independent of their specific restriction activity. hA3G was found to be a potent inhibitor of XMRV as well as of MoMLV infectivity. In contrast to MoMLV, XMRV infection can also be partially reduced by low concentrations of mA3. Interestingly, established prostate cancer cell lines, which are highly susceptible to XMRV infection, do not or only weakly express hA3G. Our findings confirm and extend recently published data that show restriction of XMRV infection by hA3G. The results will be of value to explore which cells are infected with XMRV and efficiently support viral spread in vivo. Furthermore, the observation that XMRV infection can be reduced by mA3 is of interest with regard to the current natural reservoir of XMRV infection.
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