Mouse embryonic stem cells inhibit murine cytomegalovirus infection through a multi-step process.
Mouse embryonic stem cells inhibit murine cytomegalovirus infection through a multi-step process.
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DOI：
10.1371/journal.pone.0017492
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发表时间：
2011-03-02
期刊：
影响因子：
3.7
通讯作者：
Tsutsui Y
中科院分区：
文献类型：
--
作者：
Kawasaki H;Kosugi I;Arai Y;Iwashita T;Tsutsui Y
在人类中，巨细胞病毒（CMV）是引起先天性中枢神经系统异常的宫内感染的最重要的感染性原因。目前，尚不清楚这一过程如何受到感染时间和妊娠早期细胞的易感性的影响。胚胎干细胞（ES）比大多数其他类型的细胞更能抵抗巨细胞病毒，尽管这种抵抗的机制尚不清楚。通过斑块分析和即时早期1 mRNA和蛋白表达的评估，我们发现小鼠ES细胞在转录点对小鼠CMV （MCMV）具有抗性。在MCMV感染的ES细胞中，用福斯克林和曲古抑素A治疗并不能使MCMV完全耐受。在延长因子-1α (EF-1α)启动子-绿色荧光蛋白（GFP）重组MCMV感染10次的ES培养中，尽管ES细胞具有相对较高的EF-1α启动子活性，但只有不到5%的细胞是GFP阳性的。MCMV基因组的定量PCR分析表明，胚胎干细胞允许MCMV DNA进入细胞核的数量比小鼠胚胎成纤维细胞（mef）少约20倍，并且这种抑制发生在多步骤中。原位杂交显示，胚胎干细胞细胞核的MCMV DNA明显少于MEF细胞核。与MEF相比，胚胎干细胞表达较少硫酸肝素、β1整合素和静脉蛋白，并且核孔较少，这似乎促进了这一事实。这可能会降低MCMV在多能干细胞（ES/诱导多能干细胞）中附着和穿过细胞膜、转运到细胞核和穿过核膜的能力。本文的研究结果为CMV易感性与细胞分化之间的关系提供了新的视角。
In humans, cytomegalovirus (CMV) is the most significant infectious cause of intrauterine infections that cause congenital anomalies of the central nervous system. Currently, it is not known how this process is affected by the timing of infection and the susceptibility of early-gestational-period cells. Embryonic stem (ES) cells are more resistant to CMV than most other cell types, although the mechanism responsible for this resistance is not well understood. Using a plaque assay and evaluation of immediate-early 1 mRNA and protein expression, we found that mouse ES cells were resistant to murine CMV (MCMV) at the point of transcription. In ES cells infected with MCMV, treatment with forskolin and trichostatin A did not confer full permissiveness to MCMV. In ES cultures infected with elongation factor-1α (EF-1α) promoter-green fluorescent protein (GFP) recombinant MCMV at a multiplicity of infection of 10, less than 5% of cells were GFP-positive, despite the fact that ES cells have relatively high EF-1α promoter activity. Quantitative PCR analysis of the MCMV genome showed that ES cells allow approximately 20-fold less MCMV DNA to enter the nucleus than mouse embryonic fibroblasts (MEFs) do, and that this inhibition occurs in a multi-step manner. In situ hybridization revealed that ES cell nuclei have significantly less MCMV DNA than MEF nuclei. This appears to be facilitated by the fact that ES cells express less heparan sulfate, β1 integrin, and vimentin, and have fewer nuclear pores, than MEF. This may reduce the ability of MCMV to attach to and enter through the cellular membrane, translocate to the nucleus, and cross the nuclear membrane in pluripotent stem cells (ES/induced pluripotent stem cells). The results presented here provide perspective on the relationship between CMV susceptibility and cell differentiation.
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影响因子：
5.4
作者：
Huber, MT;Tomazin, R;Johnson, DC
通讯作者：
Johnson, DC
DOI：
10.1073/pnas.0406821101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Feire, AL;Koss, H;Compton, T
通讯作者：
Compton, T
影响因子：
11.2
作者：
Eastham, Angela M.;Spencer, Helen;Ward, Christopher M.
通讯作者：
Ward, Christopher M.
DOI：
10.1073/pnas.89.16.7630
发表时间：
1992-08-15
影响因子：
11.1
作者：
GHAZAL, P;DEMATTEI, C;EVANS, RM
通讯作者：
EVANS, RM
影响因子：
5.4
作者：
LAFEMINA, R;HAYWARD, GS
通讯作者：
HAYWARD, GS