ArticleThe Journal of biological chemistry2019
A conserved region of nonstructural protein 1 from alphacoronaviruses inhibits host gene expression and is critical for viral virulence.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 85 citations in OpenAlex.
- Strategic variations in sarbecovirus and merbecovirus Nsp1 linker regions for translation inhibition.Nucleic acids research · 2026Article
- Development of the coronavirus reverse genetic system: Core technology for pathogenesis mechanisms research and vaccine/drug development.Virulence · 2025Review
- Binding of SARS-CoV-1/2 NSP1 to DNA Polymerase α-Primase Inhibits DNA Replication through Reduction of Interaction between DNA and DNA Polymerase α-Primase.Journal of chemical information and modeling · 2025Article
- Characterization of Gene Expression Suppression by Bovine Coronavirus Non-Structural Protein 1.Viruses · 2025Article
- Review
- Coronavirus endoribonuclease nsp15 suppresses host protein synthesis and evades PKR-eIF2α-mediated translation shutoff to ensure viral protein synthesis.PLoS pathogens · 2025Article
- HCoV-229E Mpro Suppresses RLR-Mediated Innate Immune Signalling Through Cleavage of NEMO and Through Other Mechanisms.International journal of molecular sciences · 2025Article
- Mechanism by which porcine transmissible gastroenteritis virus disrupts host innate immunity.Frontiers in immunology · 2025Review
- Protocol for CRISPR-Cas9 genome editing of a swine cell line via electroporation.STAR protocols · 2024Article
- Development and characterization of reverse genetics systems of feline infectious peritonitis virus for antiviral research.Veterinary research · 2024Article
- Human coronavirus NL63 nsp1 induces degradation of RNA polymerase II to inhibit host protein synthesis.PLoS pathogens · 2024Article
- Characterization of nsp1 Binding to the Viral RNA Leader Sequence of Severe Acute Respiratory Syndrome Coronavirus.Biochemistry · 2024Article
- Developing Next-Generation Live Attenuated Vaccines for Porcine Epidemic Diarrhea Using Reverse Genetic Techniques.Vaccines · 2024Review
- Swine acute diarrhea syndrome coronavirus Nsp1 suppresses IFN-λ1 production by degrading IRF1 via ubiquitin-proteasome pathway.Veterinary research · 2024Article
- The art of hijacking: how Nsp1 impacts host gene expression during coronaviral infections.Biochemical Society transactions · 2024Review
- Review
- Coronavirus takeover of host cell translation and intracellular antiviral response: a molecular perspective.The EMBO journal · 2024Review
- Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1.PloS one · 2024Article
- An Evolutionarily Conserved Strategy for Ribosome Binding and Host Translation Inhibition by β-coronavirus Non-structural Protein 1.Journal of molecular biology · 2023Article
- Broad antagonism of coronaviruses nsp5 to evade the host antiviral responses by cleaving POLDIP3.PLoS pathogens · 2023Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Coronaviruses are enveloped, single-stranded RNA viruses that are distributed worldwide. They include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and the human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), many of which seriously endanger human health and well-being. Only alphacoronaviruses and betacoronaviruses harbor nonstructural protein 1 (nsp1), which performs multiple functions in inhibiting antiviral host responses. The role of the C terminus of betacoronavirus nsp1 in virulence has been characterized, but the location of the alphacoronavirus nsp1 region that is important for virulence remains unclear. Here, using TGEV nsp1 as a model to explore the function of this protein in alphacoronaviruses, we demonstrate that alphacoronavirus nsp1 inhibits host gene expression. Solving the crystal structure of full-length TGEV at 1.85-Å resolution and conducting several biochemical analyses, we observed that a specific motif (amino acids 91-95) of alphacoronavirus nsp1 is a conserved region that inhibits host protein synthesis. Using a reverse-genetics system based on CRISPR/Cas9 technology to construct a recombinant TGEV in which this specific nsp1 motif was altered, we found that this mutation does not affect virus replication in cell culture but significantly reduces TGEV pathogenicity in pigs. Taken together, our findings suggest that alphacoronavirus nsp1 is an essential virulence determinant, providing a potential paradigm for the development of a new attenuated vaccine based on modified nsp1.
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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.