PDF(Pubmed)
Abstract：
Nowadays, the population is still struggling with a post-COVID19 syndrome known as long COVID, including a broad spectrum of neurological problems. There is an urgent need for a better understanding and exploration of the mechanisms of coronavirus neurotropism. For this purpose, the neurotropic strain of mouse hepatitis virus (MHV-JHM) originating from the beta-coronavirus genus, the same as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been used. The role of the cytoskeleton during virus replication in neurons in vitro was determined to understand the mechanisms of MHV-JHM neuroinfection. We have described for the first time the changes of actin filaments during MHV-JHM infection. We also observed productive replication of MHV-JHM in neurons during 168 h p.i. and syncytial cytopathic effect. We discovered that the MHV-JHM strain modulated neuronal cytoskeleton during infection, which were manifested by: (i) condensation of actin filaments in the cortical layer of the cytoplasm, (ii) formation of microtubule cisternae structures containing viral antigen targeting viral replication site (iii) formation of tunneling nanotubes used by MHV-JHM for intercellular transport. Additionally, we demonstrated that the use of cytoskeletal inhibitors have reduced virus replication in neurons, especially noscapine and nocodazole, the microtubule shortening factors.
摘要：
如今,人们仍在与一种被称为长COVID的COVID19后综合征作斗争，包括广泛的神经问题。迫切需要更好地理解和探索冠状病毒神经嗜性的机制。为此,源自β-冠状病毒属的小鼠肝炎病毒（MHV-JHM）的嗜神经毒株，与严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）相同，已被使用。确定了细胞骨架在体外神经元中病毒复制过程中的作用，以了解MHV-JHM神经感染的机制。我们首次描述了MHV-JHM感染过程中肌动蛋白丝的变化。我们还观察到MHV-JHM在168小时p.i.和合胞体细胞病变效应期间在神经元中的生产性复制。我们发现MHV-JHM菌株在感染过程中调节神经元细胞骨架，表现为：（i）细胞质皮质层中肌动蛋白丝的凝结，(ii)形成含有靶向病毒复制位点的病毒抗原的微管蓄水池结构(iii)形成MHV-JHM用于细胞间转运的隧穿纳米管。此外,我们证明了细胞骨架抑制剂的使用减少了神经元中的病毒复制，尤其是诺卡比和诺考达唑,微管缩短因子。
