Institut für Klinische und Molekulare Virologie der Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
J Gen Virol. 2011 Jul;92(Pt 7):1532-1538. doi: 10.1099/vir.0.030981-0. Epub 2011 Apr 6.
Nuclear domains 10 (ND10s) are discrete subnuclear structures that contain the three major protein components promyelocytic leukaemia protein (PML), hDaxx and Sp100. Previous studies identified the ND10-components PML and hDaxx as cellular restriction factors that independently counteract human cytomegalovirus (HCMV) infection via the repression of viral immediate-early (IE) gene expression. Consequently, we asked whether Sp100 is likewise involved in this repressive activity. Infection of Sp100 knockdown (kd) cells with HCMV resulted in a significantly increased plaque-forming ability. In addition, ablation of Sp100 led to a considerable increase in the number of IE1-expressing cells, indicating that Sp100 suppresses the initiation of viral gene expression. Next, double-kd cells, lacking either Sp100/hDaxx or Sp100/PML, were generated. Here, infection resulted in an additional enhancement in HCMV replication efficacy compared with the single-kd cells. Thus, our results further strengthen the concept that the three major ND10-components independently contribute to the cellular restriction of HCMV replication.
核小体 10（ND10）是离散的亚核结构，包含三个主要的蛋白质成分：早幼粒细胞白血病蛋白（PML）、hDaxx 和 Sp100。先前的研究表明，ND10 成分 PML 和 hDaxx 是细胞限制因子，通过抑制病毒即刻早期（IE）基因表达，独立拮抗人巨细胞病毒（HCMV）感染。因此，我们想知道 Sp100 是否同样参与这种抑制活性。用 HCMV 感染 Sp100 敲低（kd）细胞，导致斑块形成能力显著增加。此外，Sp100 的缺失导致表达 IE1 的细胞数量明显增加，表明 Sp100 抑制病毒基因表达的启动。接下来，生成了缺乏 Sp100/hDaxx 或 Sp100/PML 的双 kd 细胞。在这里，与单 kd 细胞相比，感染导致 HCMV 复制效果进一步增强。因此，我们的结果进一步加强了这样的概念，即三个主要的 ND10 成分独立地有助于细胞限制 HCMV 的复制。
