ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
SARS-CoV-2 viral protein ORF3A injures renal tubules by interacting with TRIM59 to induce STAT3 activation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- SARS-CoV-2 Orf3a protein interaction mapping using unnatural amino acid incorporation.Protein engineering, design & selection : PEDS · 2026Article
- Article
- SARS-CoV-2 encoded ORF3a interacts with YY1 to promote latent HCMV reactivation.PLoS pathogens · 2025Article
- The Role of Viral Infections in Acute Kidney Injury and Mesenchymal Stem Cell-Based Therapy.Stem cell reviews and reports · 2025Review
- Expression of NEAT1 induced by influenza virus infection is regulated by activated STAT3 and contributes to STAT3-mediated antiviral immunity.Frontiers in immunology · 2025Article
- Inhibiting the Otub1/phosphorylated STAT3 axis for the treatment of non-small cell lung cancer.Acta pharmacologica Sinica · 2025Article
- Article
- The Role of Dental-derived Stem Cell-based Therapy and Their Derived Extracellular Vesicles in Post-COVID-19 Syndrome-induced Tissue Damage.Stem cell reviews and reports · 2024Review
- Human E3 ubiquitin ligases: accelerators and brakes for SARS-CoV-2 infection.Biochemical Society transactions · 2024Review
- Zebrafish as a model organism for virus disease research: Current status and future directions.Heliyon · 2024Article
- Essential contribution of the JAK/STAT pathway to carcinogenesis, lytic infection of herpesviruses and pathogenesis of COVID‑19 (Review).Molecular medicine reports · 2024Review
- Article
- SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects.Pathogens (Basel, Switzerland) · 2024Review
- Paxlovid for hospitalized COVID-19 patients with chronic kidney disease.Antiviral research · 2023Article
- Mechanisms and treatment of COVID-19-associated acute kidney injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Role of E3 ubiquitin ligases and deubiquitinating enzymes in SARS-CoV-2 infection.Frontiers in cellular and infection microbiology · 2023Review
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Acute kidney injury occurs frequently in COVID-19 patients infected by the coronavirus SARS-CoV-2, and infection of kidney cells by this virus has been reported. However, little is known about the direct impact of the SARS-CoV-2 infection upon the renal tubular cells. We report that SARS-CoV-2 activated signal transducer and activator of transcription 3 (STAT3) signaling and caused cellular injury in the human renal tubular cell line. Mechanistically, the viral protein ORF3A of SARS-CoV-2 augmented both NF-κB and STAT3 signaling and increased the expression of kidney injury molecule 1. SARS-CoV-2 infection or expression of ORF3A alone elevated the protein level of tripartite motif-containing protein 59 (TRIM59), an E3 ubiquitin ligase, which interacts with both ORF3A and STAT3. The excessive TRIM59 in turn dissociated the phosphatase TCPTP from binding to STAT3 and hence inhibited the dephosphorylation of STAT3, leading to persistent STAT3 activation. Consistently, ORF3A induced renal injury in zebrafish and mice. In addition, expression of TRIM59 was elevated in the kidney autopsies of COVID-19 patients with acute kidney injury. Thus, the aberrant activation of STAT3 signaling by TRIM59 plays a significant role in the renal tubular cell injury caused by SARS-CoV-2, which suggests a potential targeted therapy for the renal complications of COVID-19.
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