Herpes simplex virus-1 (HSV-1) is a significant human pathogen. Upon infection, HSV-1 expresses its immediate early (IE) genes, and the IE transcription factor ICP4 (infectious cell protein-4) plays a pivotal role in initiating the downstream gene-expression cascade. Using live-cell time-lapse fluorescence microscopy, flow cytometry, qPCR, and chromatin immunoprecipitation, we quantitatively monitored the expression of ICP4 in individual cells after infection. We find that extrinsic stimuli can accelerate ICP4 kinetics without increasing ICP4 protein or mRNA levels. The accelerated ICP4 kinetics—despite unchanged steady-state ICP4 protein or mRNA level—correlate with increased HSV-1 replicative fitness. Hence, the kinetics of ICP4 functionally mirror the kinetics of the human herpesvirus cytomegalovirus IE2 “accelerator” circuit, indicating that IE accelerator circuitry is shared among the alpha and beta herpesviruses. We speculate that this circuit motif is a common evolutionary countermeasure to throttle IE expression and thereby minimize the inherent cytotoxicity of these obligate viral transactivators.

1 型单纯疱疹病毒 (HSV-1) 是一种重要的人类病原体。感染后，HSV-1 表达其立即早期 (IE) 基因，而 IE 转录因子 ICP4（感染细胞蛋白 4）在启动下游基因表达级联中发挥关键作用。使用活细胞延时荧光显微镜、流式细胞术、qPCR 和染色质免疫沉淀，我们定量监测感染后单个细胞中 ICP4 的表达。我们发现外部刺激可以加速 ICP4 动力学而不增加 ICP4 蛋白或 mRNA 水平。尽管稳态 ICP4 蛋白或 mRNA 水平未发生变化，但加速的 ICP4 动力学与 HSV-1 复制适应性的增加相关。因此，ICP4 的动力学在功能上反映了人类疱疹病毒巨细胞病毒 IE2“加速器”电路的动力学，表明 IE 加速器电路在 α 和 β 疱疹病毒之间共享。我们推测该电路基序是抑制 IE 表达的常见进化对策，从而最大限度地减少这些专性病毒反式激活子的固有细胞毒性。