DOI QR코드

DOI QR Code

Peste des petits ruminants virus infection induces endoplasmic reticulum stress and apoptosis via IRE1-XBP1 and IRE1-JNK signaling pathways

  • Shuyi Yuan (College of Coastal Agricultural Science of Guangdong Ocean University) ;
  • Yanfen Liu (College of Coastal Agricultural Science of Guangdong Ocean University) ;
  • Yun Mu (College of Coastal Agricultural Science of Guangdong Ocean University) ;
  • Yongshen Kuang (College of Coastal Agricultural Science of Guangdong Ocean University) ;
  • Shaohong Chen (College of Food Science and Technology of Guangdong Ocean University) ;
  • Yun-Tao Zhao (College of Food Science and Technology of Guangdong Ocean University) ;
  • You Liu (College of Food Science and Technology of Guangdong Ocean University)
  • 투고 : 2023.09.28
  • 심사 : 2024.01.10
  • 발행 : 2024.03.31

초록

Background: Peste des petits ruminants (PPR) is a contagious and fatal disease of sheep and goats. PPR virus (PPRV) infection induces endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR). The activation of UPR signaling pathways and their impact on apoptosis and virus replication remains controversial. Objectives: To investigate the role of PPRV-induced ER stress and the IRE1-XBP1 and IRE1-JNK pathways and their impact on apoptosis and virus replication. Methods: The cell viability and virus replication were assessed by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, immunofluorescence assay, and Western blot. The expression of ER stress biomarker GRP78, IRE1, and its downstream molecules, PPRV-N protein, and apoptosis-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. 4-Phenylbutyric acid (4-PBA) and STF-083010 were respectively used to inhibit ER stress and IRE1 signaling pathway. Results: The expression of GRP78, IRE1α, p-IRE1α, XBP1s, JNK, p-JNK, caspase-3, caspase-9, Bax and PPRV-N were significantly up-regulated in PPRV-infected cells, the expression of Bcl-2 was significantly down-regulated. Due to 4-PBA treatment, the expression of GRP78, p-IRE1α, XBP1s, p-JNK, caspase-3, caspase-9, Bax, and PPRV-N were significantly downregulated, the expression of Bcl-2 was significantly up-regulated. Moreover, in PPRV-infected cells, the expression of p-IRE1α, p-JNK, Bax, and PPRV-N was significantly decreased, and the expression of Bcl-2 was increased in the presence of STF-083010. Conclusions: PPRV infection induces ER stress and IRE1 activation, resulting in apoptosis and enhancement of virus replication through IRE1-XBP1s and IRE1-JNK pathways.

키워드

과제정보

The authors thank Hualong Deng, Xiaoyou Jiang, Puhong Ying, and Tiantian Sun, for their help in the execution of the project.

참고문헌

  1. Kumar N, Maherchandani S, Kashyap SK, Singh SV, Sharma S, Chaubey KK, et al. Peste des petits ruminants virus infection of small ruminants: a comprehensive review. Viruses. 2014;6(6):2287-2327.  https://doi.org/10.3390/v6062287
  2. Salminen A, Kaarniranta K, Kauppinen A. ER stress activates immunosuppressive network: implications for aging and Alzheimer's disease. J Mol Med (Berl). 2020;98(5):633-650. https://doi.org/10.1007/s00109-020-01904-z
  3. Liu Y, Wang M, Cheng A, Yang Q, Wu Y, Jia R, et al. The role of host eIF2α in viral infection. Virol J. 2020;17(1):112.
  4. Cheng JH, Sun YJ, Zhang FQ, Zhang XR, Qiu XS, Yu LP, et al. Newcastle disease virus NP and P proteins induce autophagy via the endoplasmic reticulum stress-related unfolded protein response. Sci Rep. 2016;6(1):24721.
  5. Wang W, Bi Z, Liu Y, Xia X, Qian J, Tan Y, et al. The H protein of attenuated canine distemper virus is degraded via endoplasmic reticulum-associated protein degradation. Front Vet Sci. 2023;10:1214318. 
  6. Xue M, Fu F, Ma Y, Zhang X, Li L, Feng L, et al. The PERK arm of the unfolded protein response negatively regulates transmissible gastroenteritis virus replication by suppressing protein translation and promoting type I interferon production. J Virol. 2018;92(15):e00431-18.
  7. Sun P, Jin J, Wang L, Wang J, Zhou H, Zhang Q, et al. Porcine epidemic diarrhea virus infections induce autophagy in Vero cells via ROS-dependent endoplasmic reticulum stress through PERK and IRE1 pathways. Vet Microbiol. 2021;253:108959.
  8. Wen B, Yang L, Guo J, Chang W, Wei S, Yu S, et al. Peste des petits ruminants virus induces ERS-mediated autophagy to promote virus replication. Vet Microbiol. 2022;270:109451.
  9. Zhang R, Lin H, You Q, Zhang Z, Bai L, Chen F, et al. Peste des petits ruminants virus upregulates STING to activate ATF6-mediated autophagy. J Virol. 2022;96(20):e0137522.
  10. Zhang W, Deng H, Liu Y, Chen S, Liu Y, Zhao Y. Antiviral effectivity of favipiravir against peste des petits ruminants virus is mediated by the JAK/STAT and PI3K/AKT pathways. Front Vet Sci. 2021;8:722840. 
  11. Brown M, Strudwick N, Suwara M, Sutcliffe LK, Mihai AD, Ali AA, et al. An initial phase of JNK activation inhibits cell death early in the endoplasmic reticulum stress response. J Cell Sci. 2016;129(12):2317-2328. 
  12. Xue M, Feng L. The role of unfolded protein response in coronavirus infection and its implications for drug design. Front Microbiol. 2021;12:808593.
  13. Zhang L, Wang A. Virus-induced ER stress and the unfolded protein response. Front Plant Sci (Lausanne). 2012;3:293.
  14. Ibrahim IM, Abdelmalek DH, Elfiky AA. GRP78: a cell's response to stress. Life Sci. 2019;226:156-163.  https://doi.org/10.1016/j.lfs.2019.04.022
  15. Zhu G, Lee AS. Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis. J Cell Physiol. 2015;230(7):1413-1420.
  16. Prajapati M, Alfred N, Dou Y, Yin X, Prajapati R, Li Y, et al. Host cellular receptors for the peste des petits ruminant virus. Viruses. 2019;11(8):11.
  17. Zhao Y, Hu N, Jiang Q, Zhu L, Zhang M, Jiang J, et al. Protective effects of sodium butyrate on rotavirus inducing endoplasmic reticulum stress-mediated apoptosis via PERK-eIF2α signaling pathway in IPEC-J2 cells. J Anim Sci Biotechnol. 2021;12(1):69.
  18. Song L, Han X, Jia C, Zhang X, Jiao Y, Du T, et al. Porcine reproductive and respiratory syndrome virus inhibits MARC-145 proliferation via inducing apoptosis and G2/M arrest by activation of Chk/Cdc25C and p53/p21 pathway. Virol J. 2018;15(1):169.
  19. Muthuraj PG, Sahoo PK, Kraus M, Bruett T, Annamalai AS, Pattnaik A, et al. Zika virus infection induces endoplasmic reticulum stress and apoptosis in placental trophoblasts. Cell Death Dis. 2021;7(1):24. 
  20. Yuan N, Song Q, Jin Y, Zhang Z, Wu Z, Sheng X, et al. Replication of standard bovine viral diarrhea strain OregonC24Va induces endoplasmic reticulum stress-mediated apoptosis of bovine trophoblast cells. Cell Stress Chaperones. 2023;28(1):49-60. https://doi.org/10.1007/s12192-022-01300-1
  21. Hu H, Tian M, Ding C, Yu S. The C/EBP homologous protein (CHOP) transcription factor functions in endoplasmic reticulum stress-induced apoptosis and microbial infection. Front Immunol. 2019;9:3083.
  22. Yoshida GJ. The interplay between apoptosis and ferroptosis mediated by ER stress. Apoptosis. 2020;25(11-12):784-785. https://doi.org/10.1007/s10495-020-01641-1
  23. Chen J, Ye C, Wan C, Li G, Peng L, Peng Y, et al. The roles of c-Jun N-terminal kinase (JNK) in infectious diseases. Int J Mol Sci. 2021;22(17):9640.
  24. Zhou YY, Li Y, Jiang WQ, Zhou LF. MAPK/JNK signalling: a potential autophagy regulation pathway. Biosci Rep. 2015;35(3):e00199.
  25. Wan Y, Chen Y, Wang T, Zhao B, Zeng W, Zhang L, et al. PPRV-induced autophagy facilitates infectious virus transmission by the exosomal pathway. J Virol. 2022;96(7):e0024422.