Interplay between nuclear tau phosphorylation and HSV-1 infection.

In this study, we investigated the effects of HSV-1 infection on tau phosphorylation in human brain cortical organoids. Our findings demonstrate that HSV-1 triggers nuclear accumulation of phosphorylated tau in neurons within the developing cortical plate as well as in neural precursor cells (NPCs) in the ventricular/subventricular-like zones of these differentiating cortical structures. Antiviral treatment effectively inhibited nuclear tau accumulation in both KOS- and 17syn+-infected organoids. Importantly, for the first time we provide evidence of a potential interaction of phosphorylated tau with HSV-1 genome. Furthermore, we ruled out the involvement of the Cyclin-dependent kinase 5 (Cdk5) in the nuclear phosphorylation of tau. Finally, we show that HSV-1 causes a significant alteration in the abundance of components of nuclear speckles and proteins known to be associated with neurodegenerative diseases.

本研究探究了1型单纯疱疹病毒（HSV-1）感染对人类大脑皮层类器官中tau蛋白磷酸化的影响。研究结果表明，HSV-1可诱导发育中皮层板内的神经元，以及这些正在分化的皮层结构的脑室/脑室下样区域内的神经前体细胞（NPCs）中磷酸化tau蛋白的核聚集。抗病毒治疗可有效抑制KOS株与17syn+株感染的类器官中的tau蛋白核聚集。值得关注的是，本研究首次提供了磷酸化tau蛋白与HSV-1基因组存在潜在相互作用的证据。此外，本研究排除了细胞周期蛋白依赖性激酶5（Cdk5）参与tau蛋白核磷酸化的可能性。最后，本研究证实HSV-1可显著改变核斑点（nuclear speckles）组分以及已知与神经退行性疾病相关的蛋白的丰度。