Muscovy duck reovirus p10.8 protein induces ER stress and apoptosis through the Bip/IRE1/XBP1 pathway

Publication date: Available online 12 December 2018Source: Veterinary MicrobiologyAuthor(s): Quanxi Wang, Mengxi Liu, Yuan Chen, Lihui Xu, Baocheng Wu, Yijan Wu, Yifan Huang, Wei-Ru Huang, Hung-Jen LiuAbstractIn the present study, the mechanisms underlying Muscovy duck reovirus (MDRV) p10.8 protein-induced ER stress and apoptosis in DF-1 cells and Muscovy duckling hepatic tissues were explored. On the fifth day post-infection, an increase in the mRNA levels of binding immunoglobulin protein (Bip) and X-box binding protein (XBP1), activation of XBP1/s, and an increase in percentage of apoptotic cells were observed in Muscovy duckling livers. The use of ER stress inducer Tunicamycin and ER stress inhibitor Tauroursodeoxycholic acid demonstrated that MDRV induces apoptosis via ER stress, leading to apoptosis. The use of Tunicamycin increased viral protein synthesis while Tauroursodeoxycholic acid reduced viral protein synthesis, suggesting that MDRV induces ER stress benefiting virus replication. The MDRV p10.8 is the major protein to induce ER stress and apoptosis. We found that p10.8 promotes the conversion of XBP1/u to XBP1/s and expands ER diameter, and increases the percentages of apoptotic cells in DF-1 and duckling liver tissues. To investigate the mechanism underlying the MDRV p10.8-induced ER stress and apoptosis, Western blot, siRNA, and co-immunoprecipitation (Co-IP) assays were performed. We found that the MDRV p10.8 protein up-regulates Bip, p-IRE1, XBP1s, and cleav...
Source: Veterinary Microbiology - Category: Veterinary Research Source Type: research

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