Herpes simplex virus-1 disarms the unfolded protein response in the early stages of infection
Herpes simplex virus-1 disarms the unfolded protein response in the early stages of infection
复制标题
DOI：
10.1007/s12192-012-0324-8
复制
发表时间：
2012-07-01
影响因子：
3.8
通讯作者：
Lu, Rui Ray
中科院分区：
文献类型：
--
作者：
Burnett, Heather F.;Audas, Timothy E.;Lu, Rui Ray
在病毒复制过程中，错误和未折叠蛋白的积累可导致内质网(ER)的应激，并触发未折叠蛋白反应(UPR)。如果不加以控制，这一过程可能会引起不利于病毒复制的细胞变化。在该报告中，我们研究了HSV-1在裂解复制过程中对UPR的影响。我们发现，在病毒感染的早期阶段，HSV-1有效地解除了UPR。在感染早期只检测到ATF6的激活，但没有检测到目标伴侣蛋白的上调。在HSV-1复制的最后阶段，eIF2α/ATF4信号臂的活性增加，这可能表明病毒粒子组装和输出完成，从而释放了对UPR的抑制。我们还发现，病毒ICP0的启动子对内质网应激有反应，这是对细胞UPR基因的明显模仿。这些结果提示HSV-1可能利用ICP0作为传感器来调节细胞的应激反应。
Accumulation of mis- and unfolded proteins during viral replication can cause stress in the endoplasmic reticulum (ER) and trigger the unfolded protein response (UPR). If unchecked, this process may induce cellular changes detrimental to viral replication. In the report, we investigated the impact of HSV-1 on the UPR during lytic replication. We found that HSV-1 effectively disarms the UPR in early stages of viral infection. Only ATF6 activation was detected during early infection, but with no upregulation of target chaperone proteins. Activity of the eIF2 alpha/ATF4 signaling arm increased at the final stage of HSV-1 replication, which may indicate completion of virion assembly and egress, thus releasing suppression of the UPR. We also found that the promoter of viral ICP0 was responsive to ER stress, an apparent mimicry of cellular UPR genes. These results suggest that HSV-1 may use ICP0 as a sensor to modulate the cellular stress response.