INRS-Institut Armand-Frappier, Laval, Québec, Canada.
INRS-Institut Armand-Frappier, Laval, Québec, Canada.
Virology. 2015 Sep;483:108-16. doi: 10.1016/j.virol.2015.04.003. Epub 2015 May 15.
Herpes simplex virus 1 (HSV-1) infection induces changes to the host cell nucleus including relocalization of the cellular protein Upstream Binding Factor (UBF) from the nucleolus to viral replication compartments (VRCs). Herein, we tested the hypothesis that UBF is recruited to VRCs to promote viral DNA replication. Surprisingly, infection of UBF-depleted HeLa cells with HSV-1 or HSV-2 produced higher viral titers compared to controls. Reduced expression of UBF also led to a progressive increase in the relative amount of HSV-1 DNA versus controls, and increased levels of HSV-1 ICP27 and TK mRNA and protein, regardless of whether viral DNA replication was inhibited or not. Our results suggest that UBF can inhibit gene expression from viral DNA prior to its replication. A similar but smaller effect on viral titers was observed in human foreskin fibroblasts. This is the first report of UBF having a restrictive effect on replication of a virus.
单纯疱疹病毒 1（HSV-1）感染会引起宿主细胞核的变化，包括细胞蛋白上游结合因子（UBF）从核仁重新定位到病毒复制区（VRC）。在此，我们测试了 UBF 被招募到 VRC 以促进病毒 DNA 复制的假说。令人惊讶的是，与对照相比，用 HSV-1 或 HSV-2 感染 UBF 耗尽的 HeLa 细胞产生了更高的病毒滴度。UBF 的表达减少也导致相对于对照，HSV-1 DNA 的相对量逐渐增加，并且 ICP27 和 TK mRNA 和蛋白的水平增加，无论是否抑制病毒 DNA 复制。我们的结果表明，UBF 可以在病毒 DNA 复制之前抑制其基因表达。在人包皮成纤维细胞中观察到类似但较小的对病毒滴度的影响。这是 UBF 对病毒复制具有限制作用的第一个报道。
