HHV-6A and HHV-6B are neurotropic viruses able to dysregulate autophagy and activate ER stress/UPR in several cell types. The appropriate functioning of these processes is required for cell homeostasis, particularly in post-mitotic cells such as neuronal cells. Interestingly, neurodegenerative diseases such as Alzheimer's disease (AD) are often accompanied by autophagy dysregulation and abnormal UPR activation. This study demonstrated for the first time that HHV-6A infection of astrocytoma cells and primary neurons reduces autophagy, increases Aβ production and activates ER stress/UPR promoting tau protein hyper-phosphorylation. Our results support previous studies suggesting that HHV-6A infection may play a role in AD and unveil the possible underlying molecular mechanisms involved.

中文翻译：

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HHV-6A感染失调自噬/ UPR相互作用，从而增加星形细胞瘤细胞以及原代神经元中β淀粉样蛋白的产生和tau磷酸化，这可能是病毒感染与阿尔茨海默氏病相关的分子机制。

HHV-6A和HHV-6B是神经营养性病毒，能够在几种细胞类型中失调自噬并激活ER应激/ UPR。这些过程的适当功能是细胞动态平衡所必需的，尤其是在有丝分裂后的细胞（例如神经元细胞）中。有趣的是，神经退行性疾病（例如阿尔茨海默氏病（AD））通常伴有自噬失调和UPR激活异常。这项研究首次证明，星形细胞瘤细胞和原代神经元的HHV-6A感染可减少自噬，增加Aβ的产生并激活ER应激/ UPR，从而促进tau蛋白的过度磷酸化。我们的结果支持以前的研究，表明HHV-6A感染可能在AD中起作用，并揭示了可能涉及的潜在分子机制。