ROS upregulation during the early phase of retroviral infection plays an important role in viral establishment in the host cell.
ROS upregulation during the early phase of retroviral infection plays an important role in viral establishment in the host cell.
复制标题
逆转录病毒感染早期的 ROS 上调对于病毒在宿主细胞中的建立起着重要作用。
DOI：
10.1099/vir.0.055228-0
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Wong,PaulKY
中科院分区：
文献类型：
--
作者：
Kim,SooJin;Wong,PaulKY
最近的研究表明，低水平的活性氧(ROS)经常调节正常的细胞内信号通路，决定细胞命运和控制细胞增殖。我们发现，神经致病逆转录病毒1感染星形胶质细胞，在感染的早期阶段，ROS水平较低。在感染的早期阶段，随着NADPH水平的下调，细胞内ROS的上调是一个独立的事件，而在1介导的细胞死亡发生的晚期，ROS的上调是不同的。载脂蛋白是一种潜在的NADPH氧化酶(NOX)抑制剂，处理后可抑制宿主细胞中Tets1病毒的建立。这些结果表明，由于NOX的激活而产生的ROS可能在导致病毒在宿主细胞中建立的病毒生命周期的早期事件中发挥重要作用。体外实验结果进一步得到体内实验的支持，表明罗布麻素的治疗降低了感染的小鼠脑中的病毒滴度，并延长了感染小鼠的寿命。这项研究为ROS如何参与逆转录病毒感染和1介导性神经退行性疾病的机制提供了第一个体外和活体证据。我们的发现侧重于逆转录病毒生命周期的早期阶段，可以更好地了解逆转录病毒的生命周期，这可能为抑制病毒复制和缓解小鼠模型的神经退行性症状提供特定的治疗靶点。
Recent studies suggest that low levels of reactive oxygen species (ROS) often modulate normal intracellular signalling pathways, determine cell fates and control cell proliferation. We found that infection of astrocytes with the neuropathogenic retrovirusts1, a mutant of Moloney murine leukemia retrovirus, upregulated ROS at low levels during the early phase of infection. This upregulation of intracellular ROS with downregulation of NADPH levels during the early phase ofts1 infection was a separate event from the upregulation of ROS during the late phase whilets1-mediated cell death occurred. The treatment of apocynin, a potential inhibitor of NADPH oxidase (NOX), inhibited establishment of thets1 virus in the host cell. These results suggested that ROS generated as a consequence of the activation of NOX may play an important role in the early events of the virus life cycle leading to the establishment of the virus in the host cell. Thein vitroresults were further supported by anin vivoexperiment which showed that the treatment of apocynin decreased viral titre in thets1-infected mouse brain and increased the lifespan of infected mice. This study provides the firstin vitroandin vivoevidence on a mechanism for how ROS are involved ints1 retrovirus infection andts1-mediated neurodegenerative disease. Our findings focusing on the early phase of thets1 retrovirus life cycle could provide a better understanding of retroviral life cycle, which may offer specific therapeutic targets for suppressing viral replication and alleviating neurodegenerative symptoms in a mouse model.