2. Academic Validation
  3. TRIM21 Promotes Oxidative Stress and Ferroptosis through the SQSTM1-NRF2-KEAP1 Axis to Increase the Titers of H5N1 Highly Pathogenic Avian Influenza Virus

TRIM21 Promotes Oxidative Stress and Ferroptosis through the SQSTM1-NRF2-KEAP1 Axis to Increase the Titers of H5N1 Highly Pathogenic Avian Influenza Virus

  • Int J Mol Sci. 2024 Mar 14;25(6):3315. doi: 10.3390/ijms25063315.
Yifan Wei 1 2 3,  Yongxia Gu 1 2 3,  Ziwei Zhou 1 2 3,  Changrong Wu 1 2 3,  Yanwei Liu 1 2 3,  Hailiang Sun 1 2 3
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
  • 2 Key Laboratory of Zoonosis Control and Prevention of Guangdong Province, South China Agricultural University, Guangzhou 510642, China.
  • 3 National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, South China Agricultural University, Guangzhou 510642, China.
PMID: 38542289 DOI: 10.3390/ijms25063315
Abstract

Tripartite motif-containing protein 21 (TRIM21) is involved in signal transduction and Antiviral responses through the ubiquitination of protein targets. TRIM21 was reported to be related to the imbalance of host cell homeostasis caused by viral Infection. Our studies indicated that H5N1 highly pathogenic avian Influenza Virus (HPAIV) Infection up-regulated TRIM21 expression in A549 cells. Western blot and qPCR results showed that knockdown of TRIM21 alleviated oxidative stress and Ferroptosis induced by H5N1 HPAIV and promoted the activation of antioxidant pathways. Co-IP results showed that TRIM21 promoted oxidative stress and Ferroptosis by regulating the SQSTM1-NRF2-KEAP1 axis by increasing SQSTM1 K63-linked polyubiquitination under the condition of HPAIV Infection. In addition, TRIM21 attenuated the inhibitory effect of antioxidant NAC on HPAIV titers and enhanced the promoting effect of Ferroptosis agonist Erastin on HPAIV titers. Our findings provide new insight into the role of TRIM21 in oxidative stress and Ferroptosis induced by viral Infection.

Keywords

NRF2; TRIM21; ferroptosis; influenza virus; oxidative stress.

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