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Rotavirus infection induces ferroptosis through NCOA4-mediated ferritinophagy in IPEC-J2 cells
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Ye Zhao1, 2, 3, Xia Dong1, 2, 3, Qingyuan Lan1, 2, 3, Luqian She1, 2, 3, Yongsheng Hu1, 2, 3, Lei Chen1, 2, 3, Mailin Gan1, 2, 3, Lili Niu1, 2, 3, Yan Wang1, 2, 3, Xiaofeng Zhou1, 2, 3, Linyuan Shen1, 2, 3, *, Li Zhu1, 2, 3, *
Journal of Animal Science and Biotechnology | 2026, 17(4) : 1927 - 1942
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Journal of Animal Science and Biotechnology | 2026, 17(4): 1927-1942
• ANIMAL GENETICS AND BREEDING •
Rotavirus infection induces ferroptosis through NCOA4-mediated ferritinophagy in IPEC-J2 cells
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Ye Zhao1, 2, 3, Xia Dong1, 2, 3, Qingyuan Lan1, 2, 3, Luqian She1, 2, 3, Yongsheng Hu1, 2, 3, Lei Chen1, 2, 3, Mailin Gan1, 2, 3, Lili Niu1, 2, 3, Yan Wang1, 2, 3, Xiaofeng Zhou1, 2, 3, Linyuan Shen1, 2, 3, *, Li Zhu1, 2, 3, *
Affiliations
  • 1State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu City 611130, China
  • 2Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu City 611130, China
  • 3Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu City 611130, China
Published: 2026-08-15 doi: 10.1186/s40104-026-01457-0
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Background

Rotavirus (RV) infection damages mature intestinal epithelial cells and is a leading cause of severe diarrhea in infants and young animals. However, the host cell death pathways involved in RV infection remain incompletely understood. This study used an RV-infected IPEC-J2 cell model and integrated transcriptomic, proteomic, and functional assays to investigate whether RV infection is associated with ferroptosis and NCOA4-mediated ferritinophagy.

Results

High-throughput sequencing and data-independent acquisition (DIA)-based quantitative proteomic analysis showed enrichment of ferroptosis, autophagy, and cell death-related signaling pathways after RV infection. Functional assays showed that RV infection was associated with intracellular Fe2+ accumulation and lipid peroxidation. The ferroptosis inducer (erastin) increased VP6 expression, whereas the ferroptosis inhibitor (Fer-1) attenuated this effect. NCOA4, a ferritinophagy receptor, was upregulated after RV infection. NCOA4 knockdown reduced RV-associated Fe2+ accumulation, ROS production, ferritin degradation-related changes, and VP6 expression, whereas NCOA4 overexpression enhanced these responses. The autophagy inhibitor (3-MA) and the lysosomal blocker (CQ) attenuated RV-associated ferroptosis markers and VP6 expression, consistent with involvement of the autophagy-lysosome pathway in ferritin turnover.

Conclusions

These findings support a model in which RV infection promotes ferroptosis-associated changes and VP6 expression through NCOA4-mediated ferritinophagy in IPEC-J2 cells. As this study was performed in vitro and did not directly measure epithelial transport, barrier function, infectious viral yield, or diarrheal outcomes, further in vivo studies are needed to determine the contribution of this pathway to RV pathogenesis.

Ferritinophagy  /  Ferroptosis  /  IPEC-J2 cell  /  NCOA4  /  Rotavirus
Ye Zhao, Xia Dong, Qingyuan Lan, Luqian She, Yongsheng Hu, Lei Chen, Mailin Gan, Lili Niu, Yan Wang, Xiaofeng Zhou, Linyuan Shen, Li Zhu. Rotavirus infection induces ferroptosis through NCOA4-mediated ferritinophagy in IPEC-J2 cells[J]. Journal of Animal Science and Biotechnology, 2026 , 17 (4) : 1927 -1942 . DOI: 10.1186/s40104-026-01457-0
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Funding
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  • National Key R&D Program of China(2024YFF1001500)
  • Sichuan Science and Technology Program(2022YFN0048; 2021YFYZ0007; 2021YFYZ0030)
  • Pig Industry Technology System Innovation Team of Sichuan Province(SCCXTD-2025-8)
  • China Agriculture Research System(CARS-35)
Appendix
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Year 2026 volume 17 Issue 4
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37
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Article Info
doi: 10.1186/s40104-026-01457-0
  • Receive Date：2025-10-16
  • Online Date：2026-08-13
  • Published：2026-08-15
Article Data
Affiliations
History
  • Received：2025-10-16
  • Accepted：2026-05-18
Funding
National Key R&D Program of China(2024YFF1001500)
Sichuan Science and Technology Program(2022YFN0048; 2021YFYZ0007; 2021YFYZ0030)
Pig Industry Technology System Innovation Team of Sichuan Province(SCCXTD-2025-8)
China Agriculture Research System(CARS-35)
Affiliations
    1State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu City 611130, China
    2Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu City 611130, China
    3Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu City 611130, China

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表12种不同金属材料的力学参数
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小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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