ArticleFrontiers in cell and developmental biology2021
ORF3a-Mediated Incomplete Autophagy Facilitates Severe Acute Respiratory Syndrome Coronavirus-2 Replication.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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71 citing papers in PubMed, 100 citations in OpenAlex.
- DNA methylation-mediated suppression of endocytosis confers resistance to duck hepatitis A virus type 3.Microbiology spectrum · 2026Article
- Exosomal ORF3a mediates lung-liver axis to dysregulate hepatic lipid metabolism in mild COVID-19.Cell discovery · 2026Article
- VPS34-mediated autophagosome-lysosome fusion facilitates classical swine fever virus replication.Journal of virology · 2025Article
- Mammalian innate antiviral defenses: beyond interferon.Journal of virology · 2025Review
- TGF-β inhibitor SB431542 suppresses SARS-CoV-2 replication through multistep inhibition.Journal of virology · 2025Article
- RAB5 is a host dependency factor for the generation of SARS-CoV-2 replication organelles.mBio · 2025Article
- Article
- The innate immune response in SARS-CoV2 infection: focus on toll-like receptor 4 in severe disease outcomes.Frontiers in immunology · 2025Review
- Acute COVID-19 and LongCOVID syndrome - molecular implications for therapeutic strategies - review.Frontiers in immunology · 2025Review
- Losartan and enalapril maleate differently influence SARS-CoV-2-infected vero cells.Scientific reports · 2024Article
- Is Autophagy a Friend or Foe in SARS-CoV-2 Infection?Viruses · 2024Review
- Post-Acute Sequelae and Mitochondrial Aberration in SARS-CoV-2 Infection.International journal of molecular sciences · 2024Review
- Loss to gain: pseudogenes in microorganisms, focusing on eubacteria, and their biological significance.Applied microbiology and biotechnology · 2024Review
- SARS-CoV-2 biology and host interactions.Nature reviews. Microbiology · 2024Review
- Regulation of Autophagosome-Lysosome Fusion by Human Viral Infections.Pathogens (Basel, Switzerland) · 2024Review
- Towards a Safer Future: Enhancing Vaccine Development to Combat Animal Coronaviruses.Vaccines · 2024Review
- Review
- SARS-CoV-2 virulence factor ORF3a blocks lysosome function by modulating TBC1D5-dependent Rab7 GTPase cycle.Nature communications · 2024Article
- Article
- Protein Quality Control Systems and ER Stress as Key Players in SARS-CoV-2-Induced Neurodegeneration.Cells · 2024Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent for the coronavirus disease 2019 (COVID-19) pandemic and there is an urgent need to understand the cellular response to SARS-CoV-2 infection. Beclin 1 is an essential scaffold autophagy protein that forms two distinct subcomplexes with modulators Atg14 and UVRAG, responsible for autophagosome formation and maturation, respectively. In the present study, we found that SARS-CoV-2 infection triggers an incomplete autophagy response, elevated autophagosome formation but impaired autophagosome maturation, and declined autophagy by genetic knockout of essential autophagic genes reduces SARS-CoV-2 replication efficiency. By screening 26 viral proteins of SARS-CoV-2, we demonstrated that expression of ORF3a alone is sufficient to induce incomplete autophagy. Mechanistically, SARS-CoV-2 ORF3a interacts with autophagy regulator UVRAG to facilitate PI3KC3-C1 (Beclin-1-Vps34-Atg14) but selectively inhibit PI3KC3-C2 (Beclin-1-Vps34-UVRAG). Interestingly, although SARS-CoV ORF3a shares 72.7% amino acid identity with the SARS-CoV-2 ORF3a, the former had no effect on cellular autophagy response. Thus, our findings provide the mechanistic evidence of possible takeover of host autophagy machinery by ORF3a to facilitate SARS-CoV-2 replication and raise the possibility of targeting the autophagic pathway for the treatment of 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 Socratic graph.