ArticleNature cell biology2024
ACE2-dependent and -independent SARS-CoV-2 entries dictate viral replication and inflammatory response during infection.
Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- SARS-CoV-2 Nsp1 suppresses the canonical NF-κB pathway by promoting ubiquitin-dependent degradation of TAK1 kinase.PLoS pathogens · 2026Article
- Dual antiviral and anti-inflammatory effects of BAY 11-7082 in SARS-CoV-2 infection via inhibition of the canonical NF-κB signaling pathway.Scientific reports · 2026Article
- The macrophage entry mechanism of SARS-CoV-2 mediated by surface CD98/TMPRSS11E complex is associated with the cellular tropism toward proinflammatory M1 and pathogenesis.Respiratory research · 2026Article
- Review
- C-terminus-outward orientation of SARS-CoV-2 envelope proteins on viral capsid enables a novel virus-cell interaction pathway.Frontiers in cellular and infection microbiology · 2026Article
- SARS-CoV-2 and HCoV-OC43 regulate host m6A modification via activation of the mTORC1 signalling pathway to facilitate viral replication.Emerging microbes & infections · 2025Article
- Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.Apoptosis : an international journal on programmed cell death · 2025Review
- Unique association of COVID-19 with increased risk of aplastic anemia among various viruses: insights from a two-sample Mendelian randomization study.Journal of translational medicine · 2025Article
- Design and Synthesis of Pyrazoline Inhibitors of SARS-CoV‑2 NSP14.ACS medicinal chemistry letters · 2025Article
- PRRSV promotes bacterial infection by remodeling actin cytoskeleton and cell membrane proteins.mBio · 2025Article
- Impact of inflammation levels on the liver during the COVID-19 pandemic: a mediation analysis.BMC public health · 2025Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- Article
- SARS-CoV-2 uptake and inflammatory response in senescent endothelial cells are regulated by the BSG/VEGFR2 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TScience advances · 2025Article
- CXCL10-dependent epithelial-vascular cross-talk for endothelial activation following SARS-CoV-2 infection.Scientific reports · 2025Article
- SARS-CoV-2 encoded ORF3a interacts with YY1 to promote latent HCMV reactivation.PLoS pathogens · 2025Article
- Marginal cytokine modulation by Schistosoma mansoni soluble egg antigen in SARS-CoV-2-infected K18-hACE2 mice.Folia parasitologica · 2025Article
- Co-infections and Reactivation of some Herpesviruses (HHV) and Measles Virus (MeV) in Egyptian Cancer Patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).Journal of the Egyptian National Cancer Institute · 2025Observational
- Basic implications on three pathways associated with SARS-CoV-2.Biomedical journal · 2025Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Excessive inflammation is the primary cause of mortality in patients with severe COVID-19, yet the underlying mechanisms remain poorly understood. Our study reveals that ACE2-dependent and -independent entries of SARS-CoV-2 in epithelial cells versus myeloid cells dictate viral replication and inflammatory responses. Mechanistically, SARS-CoV-2 NSP14 potently enhances NF-κB signalling by promoting IKK phosphorylation, while SARS-CoV-2 ORF6 exerts an opposing effect. In epithelial cells, ACE2-dependent SARS-CoV-2 entry enables viral replication, with translated ORF6 suppressing NF-κB signalling. In contrast, in myeloid cells, ACE2-independent entry blocks the translation of ORF6 and other viral structural proteins due to inefficient subgenomic RNA transcription, but NSP14 could be directly translated from genomic RNA, resulting in an abortive replication but hyperactivation of the NF-κB signalling pathway for proinflammatory cytokine production. Importantly, we identified TLR1 as a critical factor responsible for viral entry and subsequent inflammatory response through interaction with E and M proteins, which could be blocked by the small-molecule inhibitor Cu-CPT22. Collectively, our findings provide molecular insights into the mechanisms by which strong viral replication but scarce inflammatory response during the early (ACE2-dependent) infection stage, followed by low viral replication and potent inflammatory response in the late (ACE2-independent) infection stage, may contribute to COVID-19 progression.
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