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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Nuclear Retention Of Icpo In Cells Exposed To Hdac Inhibitor Or Transfected With Dna Before Infection With Herpes Simplex Virus 1
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Nuclear Retention Of Icpo In Cells Exposed To Hdac Inhibitor Or Transfected With Dna Before Infection With Herpes Simplex Virus 1

机译：单纯疱疹病毒感染前暴露于Hdac抑制剂或Dna转染的细胞中Icpo的核保留

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摘要

The α (immediate early) protein ICPO of herpes simplex virus 1 enhances the expression of genes introduced by infection or transfection. Early in infection it performs two key functions: It blocks the silencing of the viral DNA by cellular proteins and it blocks the IFN stimulated host response to infection. Between 5 and 9 h after infection, ICPO is translocated to the cytoplasm but remains dynamically associated with proteasomes. In this report we show that in permissive cells that are poor expressors of transfected genes (HEp-2, U2OS, etc.), ICPO is retained in the nucleus if the cells had been transfected with DNA and then infected. The retention is DNA dose- and size-dependent but not DNA type-dependent. Retention of ICPO is also a consequence of infection with wild-type virus concomitant with exposure of cells to sodium butyrate. ICPO is not retained in transfected/infected cells that efficiently express transfected genes (HEK293, rabbit skin cells). The retention of ICPO in the nucleus is concordant with failure to degrade PML and disperse ND10 structures, and delays in the transition to post α genes expression, translocation of components of the CoREST/REST/HDAC1 complex and histone relocation in the infected cell. The data suggest that (ⅰ) retention of ICPO is linked to its function to remodel acetylated DNA but not DNA in hetero-chromatin. This function is independent of response elements embedded in the DNA and (ⅱ) transfection-resistant cells do take up DNA but process it differently than cells that readily express transfected genes.
机译：单纯疱疹病毒1的α（早期早期）蛋白ICPO增强了感染或转染引入的基因的表达。在感染的早期，它执行两个关键功能：它阻止细胞蛋白使病毒DNA沉默，并阻止IFN刺激的宿主对感染的反应。感染后5至9小时之间，ICPO易位至细胞质，但仍与蛋白酶体动态相关。在本报告中，我们表明，在被转染的基因（HEp-2，U2OS等）表达不佳的宽容细胞中，如果先用DNA转染然后感染细胞，则ICPO保留在细胞核中。保留时间取决于DNA的剂量和大小，而不取决于DNA的类型。保留ICPO也是感染野生型病毒并伴随细胞暴露于丁酸钠的结果。 ICPO未保留在有效表达转染基因的转染/感染细胞中（HEK293，兔皮肤细胞）。 ICPO在细胞核中的保留与降解PML和分散ND10结构的失败，延迟后基因表达的过渡，CoREST / REST / HDAC1复合物成分的移位以及组蛋白在感染细胞中的移位有关。数据表明，ICPO的保留与其重塑乙酰化DNA的功能有关，而不与异染色质中的DNA重塑有关。此功能与嵌入到DNA中的响应元件无关，并且（？）抗转染细胞吸收DNA，但与容易表达转染基因的细胞的处理方式不同。

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