ArticleAutophagy2022
SARS-CoV-2 ORF3a induces RETREG1/FAM134B-dependent reticulophagy and triggers sequential ER stress and inflammatory responses during SARS-CoV-2 infection.
Article in Autophagy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- The accessory protein ORF3a hijacks the CLCC1 chloride channel to disrupt ER homeostasis in betacoronavirus pathogenesis.Cell discovery · 2026Article
- Endoplasmic reticulum stress and the unfolded protein response in lung diseases: molecular pathways and therapeutic interventions.The Journal of pathology · 2026Review
- RETREG1-Mediated Reticulophagy is Essential for Dendritic Cell Maturation and Function in Sepsis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PRRSV suppresses ER-phagy through Nsp2- and Nsp5-mediated degradation of FAM134B.Frontiers in cellular and infection microbiology · 2026Article
- Inhibition of STING-mediated antiviral innate immunity activation by CD97 via modulation of ER-phagy.Communications biology · 2025Article
- Deleterious variants in the autophagy-related gene RB1CC1/FIP200 impair immunity to SARS-CoV-2.Nature communications · 2025Article
- NF-E2-related factor 1 suppresses the expression of a spermine oxidase and the production of highly reactive acrolein.Scientific reports · 2025Article
- A live attenuated SARS-CoV-2 vaccine constructed by dual inactivation of NSP16 and ORF3a.EBioMedicine · 2025Article
- The role of programmed cell death in organ dysfunction induced by opportunistic pathogens.Critical care (London, England) · 2025Review
- Reticulophagy and viral infection.Autophagy · 2025Review
- Hidden players of COVID-19: the evolving roles of SARS-CoV-2 accessory proteins.Frontiers in immunology · 2025Review
- Characteristics and mechanisms of liver injury caused by emerging infectious diseases.Frontiers in immunology · 2025Review
- FAM134B in Cellular Homeostasis: Bridging Endoplasmic Reticulum-Phagy to Human Diseases.International journal of biological sciences · 2025Review
- The comprehensive SARS-CoV-2 'hijackome' knowledge base.Cell discovery · 2024Article
- Research progress and advances in endoplasmic reticulum stress regulation of acute kidney injury.Renal failure · 2024Review
- Does COVID-19 Trigger the Risk for the Development of Parkinson's Disease? Therapeutic Potential of Vitamin C.Molecular neurobiology · 2024Review
- PRRSV non-structural protein 5 inhibits antiviral innate immunity by degrading multiple proteins of RLR signaling pathway through FAM134B-mediated ER-phagy.Journal of virology · 2024Article
- Is Autophagy a Friend or Foe in SARS-CoV-2 Infection?Viruses · 2024Review
- Endoplasmic reticulum stress in diseases.MedComm · 2024Review
- A glimpse into viral warfare: decoding the intriguing role of highly pathogenic coronavirus proteins in apoptosis regulation.Journal of biomedical science · 2024Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-CoV-2 infections have resulted in a very large number of severe cases of COVID-19 and deaths worldwide. However, knowledge of SARS-CoV-2 infection, pathogenesis and therapy remains limited, emphasizing the urgent need for fundamental studies and drug development. Studies have shown that induction of macroautophagy/autophagy and hijacking of the autophagic machinery are essential for the infection and replication of SARS-CoV-2; however, the mechanism of this manipulation and the function of autophagy during SARS-CoV-2 infection remain unclear. In the present study, we identified ORF3a as an inducer of autophagy (in particular reticulophagy) and revealed that ORF3a localizes to the ER and induces RETREG1/FAM134B-related reticulophagy through the HMGB1-BECN1 (beclin 1) pathway. As a consequence, ORF3a induces ER stress and inflammatory responses through reticulophagy and then sensitizes cells to the acquisition of an ER stress-related early apoptotic phenotype and facilitates SARS-CoV-2 infection, suggesting that SARS-CoV-2 ORF3a hijacks reticulophagy and then disrupts ER homeostasis to induce ER stress and inflammatory responses during SARS-CoV-2 infection. These findings reveal the sequential induction of reticulophagy, ER stress and acute inflammatory responses during SARS-CoV-2 infection and imply the therapeutic potential of reticulophagy and ER stress-related drugs for COVID-19.
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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.