Overexpression of TRIM16 Reduces the Titer of H5N1 Highly Pathogenic Avian Influenza Virus and Promotes the Expression of Antioxidant Genes Through Regulating the SQSTM1-NRF2-KEAP1 Axis

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2023 Feb 28

PMID 36851605

Authors

Yanwei Liu

Yifan Wei

Ziwei Zhou

Yongxia Gu

Zifeng Pang

Ming Liao

Hailiang Sun

Affiliations

Soon will be listed here.

Abstract

Oxidative stress plays a vital role in viral replication. Tripartite motif containing 16 (TRIM16) is involved in diverse cellular processes. However, the role of TRIM16 in oxidative stress induced by infection of the highly pathogenic H5N1 avian influenza virus (HPAIV) is unclear. We found that under conditions of H5N1 HPAIV infection, reactive oxygen species (ROS) levels in A549 cells peaked at 24 h post infection (hpi), and antioxidant genes' expression levels were down-regulated. Overexpression of TRIM16 in A549 cells resulted in a decrease in the titter of H5N1 HPAIV and led to significant up-regulation of the antioxidant genes' expression levels, which indicates that TRIM16 positively regulates the sequestosome 1/Kelch-like associated enoyl-CoA hydratase 1 protein/nuclear factor erythrocyte 2-derived 2-like 2 (SQSTM1/NRF2/KEAP1) pathway. Under basal conditions, TRIM16 led to a modification of NRF2 through an increase in K63-linked poly-ubiquitination of NRF2. Collectively, our findings provide new insight into understanding TRIM16's role in anti-oxidative stress in H5N1 HPAIV infected A549 cells.

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References

Nazio F, Strappazzon F, Antonioli M, Bielli P, Cianfanelli V, Bordi M . mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat Cell Biol. 2013; 15(4):406-16. DOI: 10.1038/ncb2708. View

Komatsu M, Waguri S, Koike M, Sou Y, Ueno T, Hara T . Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell. 2007; 131(6):1149-63. DOI: 10.1016/j.cell.2007.10.035. View

Hu W, Liu D, Li R, Qian H, Qiu W, Ye Q . Comprehensive Analysis of TRIM Family Genes in Hepatitis Virus B-Related Hepatoma Carcinoma. Front Genet. 2022; 13:913743. PMC: 9301387. DOI: 10.3389/fgene.2022.913743. View

Choi K, Choi H, Lee J, Im S, Zhang H, Jeong Y . The endothelial E3 ligase HECW2 promotes endothelial cell junctions by increasing AMOTL1 protein stability via K63-linked ubiquitination. Cell Signal. 2016; 28(11):1642-51. DOI: 10.1016/j.cellsig.2016.07.015. View

Pakos-Zebrucka K, Koryga I, Mnich K, Ljujic M, Samali A, Gorman A . The integrated stress response. EMBO Rep. 2016; 17(10):1374-1395. PMC: 5048378. DOI: 10.15252/embr.201642195. View

Bianchi M, Giacomini E, Crinelli R, Radici L, Carloni E, Magnani M . Dynamic transcription of ubiquitin genes under basal and stressful conditions and new insights into the multiple UBC transcript variants. Gene. 2015; 573(1):100-9. DOI: 10.1016/j.gene.2015.07.030. View

Kosmider B, Messier E, Janssen W, Nahreini P, Wang J, Hartshorn K . Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus. Respir Res. 2012; 13:43. PMC: 3520784. DOI: 10.1186/1465-9921-13-43. View

Li K, Guan Y, Wang J, Smith G, Xu K, Duan L . Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature. 2004; 430(6996):209-13. DOI: 10.1038/nature02746. View

Marzioni D, Mazzucchelli R, Fantone S, Tossetta G . NRF2 modulation in TRAMP mice: an in vivo model of prostate cancer. Mol Biol Rep. 2022; 50(1):873-881. DOI: 10.1007/s11033-022-08052-2. View

10.

Hayyan M, Hashim M, AlNashef I . Superoxide Ion: Generation and Chemical Implications. Chem Rev. 2016; 116(5):3029-85. DOI: 10.1021/acs.chemrev.5b00407. View

11.

Choi Y, Jiang Z, Shin W, Jung J . Severe Fever with Thrombocytopenia Syndrome Virus NSs Interacts with TRIM21 To Activate the p62-Keap1-Nrf2 Pathway. J Virol. 2019; 94(6). PMC: 7158713. DOI: 10.1128/JVI.01684-19. View

12.

Motohashi H, Yamamoto M . Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med. 2004; 10(11):549-57. DOI: 10.1016/j.molmed.2004.09.003. View

13.

Soucy-Faulkner A, Mukawera E, Fink K, Martel A, Jouan L, Nzengue Y . Requirement of NOX2 and reactive oxygen species for efficient RIG-I-mediated antiviral response through regulation of MAVS expression. PLoS Pathog. 2010; 6(6):e1000930. PMC: 2880583. DOI: 10.1371/journal.ppat.1000930. View

14.

Python F, Goebel C, Aeby P . Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009; 239(3):273-83. DOI: 10.1016/j.taap.2009.06.003. View

15.

Narayanan A, Amaya M, Voss K, Chung M, Benedict A, Sampey G . Reactive oxygen species activate NFκB (p65) and p53 and induce apoptosis in RVFV infected liver cells. Virology. 2014; 449:270-86. DOI: 10.1016/j.virol.2013.11.023. View

16.

Akaike T, Noguchi Y, Ijiri S, Setoguchi K, Suga M, Zheng Y . Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals. Proc Natl Acad Sci U S A. 1996; 93(6):2448-53. PMC: 39817. DOI: 10.1073/pnas.93.6.2448. View

17.

Noguchi N . Role of oxidative stress in adaptive responses in special reference to atherogenesis. J Clin Biochem Nutr. 2008; 43(3):131-8. PMC: 2581764. DOI: 10.3164/jcbn.2008068. View

18.

Imai Y, Kuba K, Neely G, Yaghubian-Malhami R, Perkmann T, van Loo G . Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008; 133(2):235-49. PMC: 7112336. DOI: 10.1016/j.cell.2008.02.043. View

19.

Kobayashi M, Li L, Iwamoto N, Nakajima-Takagi Y, Kaneko H, Nakayama Y . The antioxidant defense system Keap1-Nrf2 comprises a multiple sensing mechanism for responding to a wide range of chemical compounds. Mol Cell Biol. 2008; 29(2):493-502. PMC: 2612520. DOI: 10.1128/MCB.01080-08. View

20.

Copple I, Lister A, Obeng A, Kitteringham N, Jenkins R, Layfield R . Physical and functional interaction of sequestosome 1 with Keap1 regulates the Keap1-Nrf2 cell defense pathway. J Biol Chem. 2010; 285(22):16782-8. PMC: 2878012. DOI: 10.1074/jbc.M109.096545. View