ArticleDevelopmental cell2021
ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated assembly of the SNARE complex required for autolysosome formation.
Article in Developmental cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 257 papers, 1 of them a synthesis that pooled it.
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Who cites it
257 citing papers in PubMed, 1 synthesis or guideline pooled it, 360 citations in OpenAlex.
- Time Series Analysis of SARS-CoV-2 Genomes and Correlations among Highly Prevalent Mutations.Microbiology spectrum · 2022Pooled it
- VPS33A and VPS18 orchestrate porcine epidemic diarrhea virus replication by modulating autophagic flux.Virulence · 2026Article
- The accessory protein ORF3a hijacks the CLCC1 chloride channel to disrupt ER homeostasis in betacoronavirus pathogenesis.Cell discovery · 2026Article
- Circulating cholesterol fuels SARS-CoV-2 replication via ORF3a.EMBO reports · 2026Article
- Positive-Sense RNA Viruses Reprogramming Membrane Contact Sites to Remodel Organelles and Control Cell Fate.Viruses · 2026Review
- SARS-CoV-2 Delta variant-specific ORF3a mutations destabilize lysosomal homeostasis to trigger lysosomal damage-mediated cell death.Communications biology · 2026Article
- Article
- Glycoprotein-induced phase separation drives unconventional secretion of galectin-3.Nature communications · 2026Article
- The cell with many faces: lung macrophage plasticity and function in response to environmental and pathogenic insults.Physiological reviews · 2026Review
- Review
- SARS-CoV-2 ORF3a blocks lysosomal cholesterol egress by disrupting VPS39-regulated NPC2 trafficking and BMP metabolism.Cell reports · 2026Article
- Coronavirus protein interaction mapping in bat and human cells reveals network rewiring governing immune evasion and zoonotic potential.Cell host & microbe · 2026Article
- BST-2 inhibits SARS-CoV-2 egress at intracellular membranes and is neutralized by ORF7a.Scientific reports · 2026Article
- Supervised deep learning with gene functional annotation for cell classification.PLoS computational biology · 2026Article
- Exosomal ORF3a mediates lung-liver axis to dysregulate hepatic lipid metabolism in mild COVID-19.Cell discovery · 2026Article
- Inhibition of host N-myristoylation compromises the infectivity of SARS-CoV-2 due to Golgi-bypassing egress.Nature communications · 2026Article
- Pathogen-Induced Lysosomal Membrane Permeabilization: A Critical Interface Between Host Defense and Cell Death.International journal of molecular sciences · 2026Review
- A murine coronavirus infection platform identifies proviral and proinflammatory activities of SARS-CoV-2 accessory protein 7a.Journal of virology · 2026Article
- SNX-3 confers lysosomal fusion-competence to sustain basal autophagy.Cellular and molecular life sciences : CMLS · 2026Article
- Tetrandrine-driven autophagy suppresses SARS-CoV-2 replication by modulating cholesterol and IGF signaling pathways.Cell death discovery · 2026Article
197 more citing papers are in PubMed but not listed here.
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9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy acts as a cellular surveillance mechanism to combat invading pathogens. Viruses have evolved various strategies to block autophagy and even subvert it for their replication and release. Here, we demonstrated that ORF3a of the COVID-19 virus SARS-CoV-2 inhibits autophagy activity by blocking fusion of autophagosomes/amphisomes with lysosomes. The late endosome-localized ORF3a directly interacts with and sequestrates the homotypic fusion and protein sorting (HOPS) component VPS39, thereby preventing HOPS complex from interacting with the autophagosomal SNARE protein STX17. This blocks assembly of the STX17-SNAP29-VAMP8 SNARE complex, which mediates autophagosome/amphisome fusion with lysosomes. Expression of ORF3a also damages lysosomes and impairs their function. SARS-CoV-2 virus infection blocks autophagy, resulting in accumulation of autophagosomes/amphisomes, and causes late endosomal sequestration of VPS39. Surprisingly, ORF3a from the SARS virus SARS-CoV fails to interact with HOPS or block autophagy. Our study reveals a mechanism by which SARS-CoV-2 evades lysosomal destruction and provides insights for developing new strategies to treat 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.