ArticleProceedings of the National Academy of Sciences of the United States of America2020
SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 386 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
386 citing papers in PubMed, 1 synthesis or guideline pooled it, 557 citations in OpenAlex.
- Defining the Clinicoradiologic Syndrome of SARS-CoV-2 Acute Necrotizing Encephalopathy: A Systematic Review and 3 New Pediatric CasesNeurology(R) neuroimmunology & neuroinflammation · 2024Pooled it
- The diverse functions of viral microproteins.bioRxiv : the preprint server for biology · 2026Article
- Molecular Insights into High-Pathogenicity RNA Viruses.Viruses · 2026Review
- Temporal Dynamics of Innate Immune Activation and Viral Interference During Sequential Co-Infection with Influenza A Virus and SARS-CoV-2: Molecular Mechanisms, Clinical Evidence, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Spatial Immune Model of Alveolar Lung Infection (SIMALI) Identifies Structural Determinants of Lung Inflammation.Research square · 2026Article
- Targeting SARS-CoV-2 Structural and Accessory Proteins: Emerging Opportunities for Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Modulation of Host Innate Immune Response by Highly Pathogenic Human Coronaviruses during Viral Infection.Journal of microbiology and biotechnology · 2026Review
- SARS-CoV-2 Nsp1 suppresses the canonical NF-κB pathway by promoting ubiquitin-dependent degradation of TAK1 kinase.PLoS pathogens · 2026Article
- Tripartite motif-containing 34 (TRIM34) protein interacts with the nucleocytoplasmic transport machinery and negatively modulates antiviral responses.PLoS pathogens · 2026Article
- Single-cell polygenic risk scores dissect cellular and molecular heterogeneity of complex human diseases.Nature biotechnology · 2026Article
- Redundant and distinct mechanisms suppress innate immune activation during SARS-CoV-2 infection.PLoS biology · 2026Article
- Leveraging ADMET Profiling, Network Pharmacology, and Molecular Docking to Evaluate the Repurposing of Product Nkabinde for COVID-19 Treatment.Biomedicines · 2026Article
- SARS-CoV-2 nonstructural protein 3 remodels the phosphorylation of target proteins via protein-protein interactions.Microbiology spectrum · 2026Article
- Genetic and chemical correction of cystic fibrosis reduces airway susceptibility to SARS-CoV-2.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Review
- The ORF6 accessory protein contributes to SARS-CoV-2 virulence and pathogenicity in the naturally susceptible feline model of infection.Journal of virology · 2026Article
- Zooming into Disease at the Nanoscale: High-Speed Atomic Force Microscopy in Biomedical Discovery.ACS nano · 2026Review
- Effectiveness of COVID-19 Vaccination in Reducing Severity Among SARS-CoV-2 Infected Patients: A Prospective Study From Iraq.Health science reports · 2026Article
- Breaking barriers: Respiratory viral strategies targeting the host's nuclear pore complex and nuclear transport pathways.Molecular biology of the cell · 2026Review
- NUP98 regulates orthoflavivirus replication through interaction with vRNA and can be targeted for antiviral purposes.Nucleic acids research · 2026Article
326 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 6 institutions in 2 countries.
Funding
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that is a serious global health problem. Evasion of IFN-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in their host. In this study, we show that SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of IFN-stimulated genes (ISGs). Our results demonstrate that the viral accessory protein Orf6 exerts this anti-IFN activity. We found that SARS-CoV-2 Orf6 localizes at the nuclear pore complex (NPC) and directly interacts with Nup98-Rae1 via its C-terminal domain to impair docking of cargo-receptor (karyopherin/importin) complex and disrupt nuclear import. In addition, we show that a methionine-to-arginine substitution at residue 58 impairs Orf6 binding to the Nup98-Rae1 complex and abolishes its IFN antagonistic function. All together our data unravel a mechanism of viral antagonism in which a virus hijacks the Nup98-Rae1 complex to overcome the antiviral action of IFN.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.