ArticleAutophagy2022
Protein disulfide isomerases (PDIs) negatively regulate ebolavirus structural glycoprotein expression in the endoplasmic reticulum (ER) via the autophagy-lysosomal pathway.
Article in Autophagy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Intracellular pathogen manipulation of ER-phagy: direct receptor targeting and indirect pathway perturbation.Medical microbiology and immunology · 2026Review
- Mapping the global evidence base of bundibugyo ebolavirus disease: a systematic scoping review of research gaps and preparedness priorities.BMC infectious diseases · 2026Article
- FAM134B isoform 2/RETREG1-2 defines a calnexin-TOLLIP-coupled ER-phagy pathway that restricts Ebola virus glycoprotein and is antagonized by VP40 through macro-autophagy.bioRxiv : the preprint server for biology · 2026Article
- Irgm1 Improves Postinfarction Cardiac Repair by Promoting Neutrophil Clearance and Efferocytosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bioinformatic Prediction of Activation States in Molecular Network Pathways of Eukaryotic Initiation Factor 2 (EIF2) Signaling and Coronavirus Pathogenesis.International journal of molecular sciences · 2026Article
- Activating transcription factors: Orchestrators of macrophage biology in pathological settings (Review).International journal of molecular medicine · 2026Review
- Membralin Assembles a MAN1B1-VCP Complex to Target Foreign Glycoproteins from the Endoplasmic Reticulum to Lysosomes for Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Autophagy regulation and viral exploitation: insights into African swine fever virus pathogenesis.Frontiers in cellular and infection microbiology · 2026Review
- Autophagy in emerging and highly concerned severe zoonotic infectious diseases.Frontiers in immunology · 2026Review
- Murine leukemia virus glycoGag antagonizes SERINC5 via ER-phagy receptor RETREG1.PLoS pathogens · 2025Article
- Article
- A cellular model of TDP-43 induces phosphorylated TDP-43 aggregation with distinct changes in solubility and autophagy dysregulation.The FEBS journal · 2025Article
- AP3B1 facilitates PDIA3/ERP57 function to regulate rabies virus glycoprotein selective degradation and viral entry.Autophagy · 2024Article
- Endoplasmic reticulum stress in diseases.MedComm · 2024Review
- Furin Egress from the TGN is Regulated by Membrane-Associated RING-CH Finger (MARCHF) Proteins and Ubiquitin-Specific Protease 32 (USP32) via Nondegradable K33-Polyubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
- The relationship between autophagy and respiratory viruses.Archives of microbiology · 2024Review
- Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy.Cell communication and signaling : CCS · 2024Review
- Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1.Nature communications · 2024Article
- The role of PDIA3 in oral squamous cell carcinoma and its value as A diagnostic and prognostic biomarker.Heliyon · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zaire ebolavirus (EBOV) causes a severe hemorrhagic fever in humans and non-human primates with high morbidity and mortality. EBOV infection is dependent on its structural glycoprotein (GP), but high levels of GP expression also trigger cell rounding, detachment, and downregulation of many surface molecules that is thought to contribute to its high pathogenicity. Thus, EBOV has evolved an RNA editing mechanism to reduce its GP expression and increase its fitness. We now report that the GP expression is also suppressed at the protein level in cells by protein disulfide isomerases (PDIs). Although PDIs promote oxidative protein folding by catalyzing correct disulfide formation in the endoplasmic reticulum (ER), PDIA3/ERp57 adversely triggered the GP misfolding by targeting GP cysteine residues and activated the unfolded protein response (UPR). Abnormally folded GP was targeted by ER-associated protein degradation (ERAD) machinery and, unexpectedly, was degraded via the macroautophagy/autophagy-lysosomal pathway, but not the proteasomal pathway. PDIA3 also decreased the GP expression from other ebolavirus species but increased the GP expression from Marburg virus (MARV), which is consistent with the observation that MARV-GP does not cause cell rounding and detachment, and MARV does not regulate its GP expression via RNA editing during infection. Furthermore, five other PDIs also had a similar inhibitory activity to EBOV-GP. Thus, PDIs negatively regulate ebolavirus glycoprotein expression, which balances the viral life cycle by maximizing their infection but minimizing their cellular effect. We suggest that ebolaviruses hijack the host protein folding and ERAD machinery to increase their fitness via reticulophagy during infection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.