State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, China.
Viruses. 2019 Feb 1;11(2):133. doi: 10.3390/v11020133.
To understand the underlying mechanisms of endoplasmic reticulum (ER) stress caused by human rhinovirus (HRV) 16 and non-structural transmembrane protein 2B, the expressions of ER chaperone glucose-regulated protein 78 (GRP78) and three signal transduction pathways, including protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1 (IRE1), were evaluated after HRV16 infection and 2B gene transfection. Our results showed that both HRV16 infection and 2B gene transfection increased the expression of ER chaperone GRP78, and induced phosphorylation of PERK and cleavage of ATF6 in a time-dependent manner. Our data also revealed that the HRV16 2B protein was localized to the ER membrane. However, both HRV16 infection and HRV16 2B gene transfection did not induce ER stress through the IRE1 pathway. Moreover, our results showed that apoptosis occurred in H1-HeLa cells infected with HRV16 or transfected with 2B gene accompanied with increased expression of CHOP and cleaved caspase-3. Taken together, non-structural protein 2B of HRV16 induced an ER stress response through the PERK and ATF6 pathways rather than the IRE1 pathway.
为了了解人鼻病毒（HRV）16 和非结构跨膜蛋白 2B 引起内质网（ER）应激的潜在机制，评估了 HRV16 感染和 2B 基因转染后 ER 伴侣葡萄糖调节蛋白 78（GRP78）的表达和三条信号转导通路，包括蛋白激酶 RNA 样内质网激酶（PERK）、激活转录因子 6（ATF6）和肌醇需求酶 1（IRE1）。结果表明，HRV16 感染和 2B 基因转染均增加了 ER 伴侣 GRP78 的表达，并呈时间依赖性诱导 PERK 的磷酸化和 ATF6 的切割。我们的数据还表明，HRV16 2B 蛋白定位于 ER 膜。然而，HRV16 感染和 HRV16 2B 基因转染均未通过 IRE1 通路诱导 ER 应激。此外，我们的结果表明，感染 HRV16 或转染 2B 基因的 H1-HeLa 细胞发生了凋亡，伴随着 CHOP 和 cleaved caspase-3 的表达增加。总之，HRV16 的非结构蛋白 2B 通过 PERK 和 ATF6 途径而不是 IRE1 途径诱导 ER 应激反应。
