ArticleRedox biology2019
Lung epithelial protein disulfide isomerase A3 (PDIA3) plays an important role in influenza infection, inflammation, and airway mechanics.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
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- CysDBase: a comprehensive database of cysteine post-translational modifications across protein sequence, structure, microenvironment, class, cellular localization, biological pathway, and taxonomy.Database : the journal of biological databases and curation · 2026Article
- The leader of the capsid protein fromJournal of virology · 2025Article
- Effects of oxidative stress on viral infections: an overview.Npj viruses · 2025Review
- Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets.Frontiers in immunology · 2025Review
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- AP3B1 facilitates PDIA3/ERP57 function to regulate rabies virus glycoprotein selective degradation and viral entry.Autophagy · 2024Article
- The protein disulfide isomerase A3 and osteopontin axis promotes influenza-induced lung remodelling.British journal of pharmacology · 2024Article
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- Inclusive Pattern Generation Protocols to Decode Thiol-Mediated Uptake.ACS central science · 2024Article
- The small molecule CBR-5884 inhibits themBio · 2024Article
- Hepatitis E virus ORF3 protein hijacking thioredoxin domain-containing protein 5 (TXNDC5) for its stability to promote viral particle release.Journal of virology · 2024Article
- Co-evolution of SARS-CoV-2 variants and host immune response trajectories underlie COVID-19 pandemic to epidemic transition.iScience · 2023Article
- Structural and functional fine mapping of cysteines in mammalian glutaredoxin reveal their differential oxidation susceptibility.Nature communications · 2023Article
- Biochemical mechanism of erastin-induced ferroptotic cell death in neuronal cells.Acta biochimica et biophysica Sinica · 2023Article
- Redox proteomics and structural analyses provide insightful implications for additional non-catalytic thiol-disulfide motifs in PDIs.Redox biology · 2023Article
- Inflammation in Pulmonary Hypertension and Edema Induced by Hypobaric Hypoxia Exposure.International journal of molecular sciences · 2022Review
- Proteomic profiling of serum small extracellular vesicles reveals immune signatures of children with pneumonia.Translational pediatrics · 2022Article
- Quantitative Proteomic Analysis Reveals Important Roles of the Acetylation of ER-Resident Molecular Chaperones for Conidiation in Fusarium oxysporum.Molecular & cellular proteomics : MCP · 2022Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein disulfide isomerases (PDI) are a family of redox chaperones that catalyze formation or isomerization of disulfide bonds in proteins. Previous studies have shown that one member, PDIA3, interacts with influenza A virus (IAV) hemagglutinin (HA), and this interaction is required for efficient oxidative folding of HA in vitro. However, it is unknown whether these host-viral protein interactions occur during active infection and whether such interactions represent a putative target for the treatment of influenza infection. Here we show that PDIA3 is specifically upregulated in IAV-infected mouse or human lung epithelial cells and PDIA3 directly interacts with IAV-HA. Treatment with a PDI inhibitor, LOC14 inhibited PDIA3 activity in lung epithelial cells, decreased intramolecular disulfide bonds and subsequent oligomerization (maturation) of HA in both H1N1 (A/PR8/34) and H3N2 (X31, A/Aichi/68) infected lung epithelial cells. These reduced disulfide bond formation significantly decreased viral burden, and also pro-inflammatory responses from lung epithelial cells. Lung epithelial-specific deletion of PDIA3 in mice resulted in a significant decrease in viral burden and lung inflammatory-immune markers upon IAV infection, as well as significantly improved airway mechanics. Taken together, these results indicate that PDIA3 is required for effective influenza pathogenesis in vivo, and pharmacological inhibition of PDIs represents a promising new anti-influenza therapeutic strategy during pandemic and severe influenza seasons.
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