ArticleNature communications2024
SARS-CoV-2 virulence factor ORF3a blocks lysosome function by modulating TBC1D5-dependent Rab7 GTPase cycle.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
42 citing papers in PubMed, 46 citations in OpenAlex.
- 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
- SARS-CoV-2 Delta variant-specific ORF3a mutations destabilize lysosomal homeostasis to trigger lysosomal damage-mediated cell death.Communications biology · 2026Article
- Arl8b inactivates the Rab11a recycling pathway to promote LAMP1 sorting and lysosome biogenesis.The Journal of cell biology · 2026Article
- SARS-CoV-2 ORF3a blocks lysosomal cholesterol egress by disrupting VPS39-regulated NPC2 trafficking and BMP metabolism.Cell reports · 2026Article
- VPS33B regulates MHC class II antigen presentation in dendritic cells to drive CD4 T cell immunity.iScience · 2026Article
- ARF-like GTPase 8B orchestrates lipophagy and exocytosis to drive single-stranded RNA virus replication.Journal of translational medicine · 2026Article
- Targeting SARS-CoV-2 Structural and Accessory Proteins: Emerging Opportunities for Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- BST-2 inhibits SARS-CoV-2 egress at intracellular membranes and is neutralized by ORF7a.Scientific reports · 2026Article
- Inhibition of host N-myristoylation compromises the infectivity of SARS-CoV-2 due to Golgi-bypassing egress.Nature communications · 2026Article
- Review
- Extracellular Vesicle-Delivered tRF-His-GTG-1 Reprograms Neutrophil Lipophagy and Triggers Inflammation in COVID-19.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A murine coronavirus infection platform identifies proviral and proinflammatory activities of SARS-CoV-2 accessory protein 7a.Journal of virology · 2026Article
- Article
- From HIV to SARS-CoV-2 associated neurological disorder ("HAND" to "SAND"): Viral infection as a "time-bomb" for the aging brain.Neuroscience applied · 2026Review
- ClinIAN: Clinically Informed Attention Network.Bioinformatics advances · 2026Article
- ORF3 Depletion Attenuates SADS-CoV Virulence and Retains Partial Maternally Mediated Protection in Suckling Mice.Transboundary and emerging diseases · 2026Article
- The neuropathy-linked protein TECPR2 is a Rab5 effector that regulates cargo recycling from early endosomes.Nature communications · 2025Article
- TGF-β inhibitor SB431542 suppresses SARS-CoV-2 replication through multistep inhibition.Journal of virology · 2025Article
- SARS-CoV-2 ORF3a blocks lysosomal cholesterol egress by disrupting VPS39-regulated NPC2 trafficking and BMP metabolism.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
SARS-CoV-2, the causative agent of COVID-19, uses the host endolysosomal system for entry, replication, and egress. Previous studies have shown that the SARS-CoV-2 virulence factor ORF3a interacts with the lysosomal tethering factor HOPS complex and blocks HOPS-mediated late endosome and autophagosome fusion with lysosomes. Here, we report that SARS-CoV-2 infection leads to hyperactivation of the late endosomal and lysosomal small GTP-binding protein Rab7, which is dependent on ORF3a expression. We also observed Rab7 hyperactivation in naturally occurring ORF3a variants encoded by distinct SARS-CoV-2 variants. We found that ORF3a, in complex with Vps39, sequesters the Rab7 GAP TBC1D5 and displaces Rab7 from this complex. Thus, ORF3a disrupts the GTP hydrolysis cycle of Rab7, which is beneficial for viral production, whereas the Rab7 GDP-locked mutant strongly reduces viral replication. Hyperactivation of Rab7 in ORF3a-expressing cells impaired CI-M6PR retrieval from late endosomes to the trans-Golgi network, disrupting the biosynthetic transport of newly synthesized hydrolases to lysosomes. Furthermore, the tethering of the Rab7- and Arl8b-positive compartments was strikingly reduced upon ORF3a expression. As SARS-CoV-2 egress requires Arl8b, these findings suggest that ORF3a-mediated hyperactivation of Rab7 serves a multitude of functions, including blocking endolysosome formation, interrupting the transport of lysosomal hydrolases, and promoting viral egress.
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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.