RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis

Li, Yingguang; Bao, Yuwei; Li, Yan; Duan, Xiaoxiao; Dong, Shaoming; Lin, Jiaxu; Chang, Xiaoyun; Tan, Yue; Zhang, Hongliang; Shan, Hu

doi:10.3390/v15102080

Cited by 6 publications

(4 citation statements)

References 41 publications

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“…Ferroptosis is one type of regulatory cell death, which is an important strategy for host cells to resist pathogen invasion. RSL3 is a ferroptosis inducer that has been reported to inhibit the proliferation of porcine epidemic diarrhea virus (PEDV) in Vero cells [ 55 ]. Brequinar activates ferroptosis to inhibit ASFV replication [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

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

Wei,

Gu,

Zhou

et al. 2024

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

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

Wei,

Gu,

Zhou

et al. 2024

IJMS

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“…The commonly used class II ferroptosis inducers are RAS-selective lethal 3 (RSL3) ( 127 ), 2-chloro-N-(3-chloro-4-methoxyphenyl)-N-(2-oxo-2-(phenethylamino)-1-(thiophen-2-yl)ethyl)acetamide ( 128 ) and cisplatin (which binds to GSH and inactivates GPX4) ( 129 ). However, the most commonly used class II ferroptosis inducer is RSL3, predominantly since RSL3 is an inducer that can either indirectly or directly induce the occurrence of ferroptosis ( 130 ).…”

Section: Ferroptosis Inducers and Strokementioning

confidence: 99%

Recent advances in potential therapeutic targets of ferroptosis‑associated pathways for the treatment of stroke (Review)

Dong,

Ma,

Cui

et al. 2024

Mol Med Rep

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Stroke is a severe neurological disease that is associated with high rates of morbidity and mortality, and the underlying pathological processes are complex. Ferroptosis fulfills a significant role in the progression and treatment of stroke. It is well established that ferroptosis is a type of programmed cell death that is distinct from other forms or types of cell death. The process of ferroptosis involves multiple signaling pathways and regulatory mechanisms that interact with mechanisms inherent to stroke development. Inducers and inhibitors of ferroptosis have been shown to exert a role in the onset of this cell death process. Furthermore, it has been shown that interfering with ferroptosis affects the occurrence of stroke, indicating that targeting ferroptosis may offer a promising therapeutic approach for treating patients of stroke. Hence, the present review aimed to summarize the latest progress that has been made in terms of using therapeutic interventions for ferroptosis as treatment targets in cases of stroke. It provides an overview of the relevant pathways and molecular mechanisms that have been investigated in recent years, highlighting the roles of inducers and inhibitors of ferroptosis in stroke. Additionally, the intervention potential of various types of Traditional Chinese Medicine is also summarized. In conclusion, the present review provides a comprehensive overview of the potential therapeutic targets afforded by ferroptosis-associated pathways in stroke, offering new insights into how ferroptosis may be exploited in the treatment of stroke.

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“…Ferroptosis is an important cellular non-apoptotic form of regulated cell death that plays a role in several viral infections (23,24). To further explore the specific role of ferroptosis pathway plays in PDCoV infection, we used erastin, a classical activator of ferroptosis (22), to pretreated with IPEC-J2 cells, and then infected with PDCoV at an MOI of 1.…”

Section: Activator Of Ferroptosis Signaling Pathway Inhibits Pdcov In...mentioning

confidence: 99%

Comprehensive transcriptomic and metabolomic analysis of porcine intestinal epithelial cells after PDCoV infection

Wang,

Cao,

et al. 2024

Front. Vet. Sci.

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IntroductionPorcine deltacoronavirus (PDCoV), an emerging swine enteropathogenic coronavirus with worldwide distribution, mainly infects newborn piglets with severe diarrhea, vomiting, dehydration, and even death, causing huge economic losses to the pig industry. However, the underlying pathogenic mechanisms of PDCoV infection and the effects of PDCoV infection on host transcripts and metabolites remain incompletely understood.MethodsThis study investigated a combined transcriptomic and metabolomic analysis of porcine intestinal epithelial cells (IPEC-J2) following PDCoV infection by LC/MS and RNA-seq techniques. A total of 1,401 differentially expressed genes and 254 differentially accumulated metabolites were detected in the comparison group of PDCoV-infected vs. mock-infected.Results and discussionWe found that PDCoV infection regulates gene sets associated with multiple signaling pathways, including the neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, MAPK signaling pathway, chemokine signaling pathway, ras signaling pathway and so on. Besides, the metabolomic results showed that biosynthesis of cofactors, nucleotide metabolism, protein digestion and absorption, and biosynthesis of amino acid were involved in PDCoV infection. Moreover, integrated transcriptomics and metabolomics analyses revealed the involvement of ferroptosis in PDCoV infection, and exogenous addition of the ferroptosis activator erastin significantly inhibited PDCoV replication. Overall, these unique transcriptional and metabolic reprogramming features may provide a better understanding of PDCoV-infected IPEC-J2 cells and potential targets for antiviral treatment.

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RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis

Cited by 6 publications

References 41 publications

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

Recent advances in potential therapeutic targets of ferroptosis‑associated pathways for the treatment of stroke (Review)

Comprehensive transcriptomic and metabolomic analysis of porcine intestinal epithelial cells after PDCoV infection

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