Evasion of antiviral innate immunity by SARS-CoV-2 NSP1 is exerted through H3K9 di-methylation
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ABSTRACT:
PROVIDER: PRJNA858420 | ENA |
REPOSITORIES: ENA
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Project description:The pathogen causing the current COVID-19 pandemic, the severe acute respiratory syndrome coronavirus (SARS-CoV-2), evades the innate immune machinery through the independent action of several viral proteins, including the nonstructural protein 1 (NSP1). NSP1 has multiple functions, but the relative contribution of NSP1-mediated translational repression, ribosome-proximate degradation of host mRNA, or other molecular mechanisms to viral immune evasion remains unclear. Here we combined several genome wide approaches, including RNA-seq, ribosome footprinting, and ChIP-seq to find that NSP1 predominantly affects transcription of immune-related genes. NSP1 expression in A549 cells induced Histone 3 Lysine 9 (H3K9) methylation of antiviral gene loci, leading to specific suppression of type I and type III interferon pathways. Treatment with the G9a/GLP H3K9 methyltransferase inhibitor UNC0638 reverses this suppression of antiviral genes and blocks viral replication after SARS-CoV2 infection of A549 cells. Our results call attention to epigenetic reprogramming induced by SARS-CoV2 and highlight the importance to identify innate factors regulating histone modification of gene loci targeted by SARS-CoV-2, with possible relevance to the understanding and therapy of other immunomodulatory diseases.
2023-07-12 | GSE208116 | GEO
Project description:Extensive remodeling of host gene expression by coronaviruses nsp1 proteins is a well-documented and conserved aspect of coronavirus-host takeover. Using comparative transcriptomics we investigate the diversity of transcriptional targets between nsp1 proteins between α- and β- coronaviruses. Additionally, Affinity Purification Mass-Spectrometry was implemented to identify common and divergent interactors between the nsp1 proteins. While we detected widespread RNA destabilization between the different nsp1s, closely related nsp1 showed little similarities in clustering of targeted genes. Partial overlapping transcriptional targeting between α-CoV 229E and MERS nsp1 may suggest a shared similar targeting mechanism, as MERS nsp1 preferentially targets nuclear transcripts. Our interactome data shows great variance between nsp1 interactions, with 229E nsp1, the smallest tested here, interacts with the most host proteins, while MERS nsp1 only engaged with a few. While nsp1 is a rather well-conserved protein with consistent functions across different coronaviruses, its precise effects on host cells is virus-specific.
2022-11-17 | GSE217848 | GEO
Project description:This study investigated the immunological function of PRRSV Nsp1 by ectopic expression of PRRSV Nsp1 in 3D4/31 cell line. Identifying the functional role of PRRSV Nsp1 associated with host cell modulation may provide better knowledge about the pathogenesis of PRRS (Porcine reproductive and respiratory syndrome).
2022-03-21 | GSE128929 | GEO
Project description:Legume GRAS-type transcription factors NSP1 and NSP2 are essential for Rhizobium Nod factor-induced nodulation. Both proteins are considered to be Nod factor response factors regulating gene expression upon symbiotic signalling. However, legume NSP1 and NSP2 can be functionally replaced by non-legume orthologs; including rice (Oryza sativa) OsNSP1 and OsNSP2. This shows that both proteins are functionally conserved in higher plants, suggesting an ancient function that was conserved during evolution. Here we show that NSP1 and NSP2 are indispensable for strigolactone biosynthesis in the legume Medicago truncatula as well as rice. Mutant nsp1-nsp2 plants hardly produce strigolactones. The lack of strigolactone biosynthesis coincides with strongly reduced DWARF27 expression in both species. Rice and Medicago represent distinct phylogenetic lineages that split ~150 million years ago. Therefore we conclude that regulation of strigolactone biosynthesis by NSP1 and NSP2 is an ancestral function conserved in higher plants. Since strigolactone biosynthesis is highly regulated by environmental conditions like phosphate starvation, NSP1 and NSP2 will be important tools in future studies on the molecular mechanisms by which environmental sensing is translated into regulation of strigolactone biosynthesis. As NSP1 and NSP2 are single copy genes in legumes, it implies that a single protein complex fulfills a dual regulatory function of different downstream targets; symbiotic and non-symbiotic, respectively. Three biological replications are used for roots of wild type A17, nsp1 and nsp2 mutant plants
2011-11-01 | E-GEOD-26548 | biostudies-arrayexpress
Project description:Legume GRAS-type transcription factors NSP1 and NSP2 are essential for Rhizobium Nod factor-induced nodulation. Both proteins are considered to be Nod factor response factors regulating gene expression upon symbiotic signalling. However, legume NSP1 and NSP2 can be functionally replaced by non-legume orthologs; including rice (Oryza sativa) OsNSP1 and OsNSP2. This shows that both proteins are functionally conserved in higher plants, suggesting an ancient function that was conserved during evolution. Here we show that NSP1 and NSP2 are indispensable for strigolactone biosynthesis in the legume Medicago truncatula as well as rice. Mutant nsp1-nsp2 plants hardly produce strigolactones. The lack of strigolactone biosynthesis coincides with strongly reduced DWARF27 expression in both species. Rice and Medicago represent distinct phylogenetic lineages that split ~150 million years ago. Therefore we conclude that regulation of strigolactone biosynthesis by NSP1 and NSP2 is an ancestral function conserved in higher plants. Since strigolactone biosynthesis is highly regulated by environmental conditions like phosphate starvation, NSP1 and NSP2 will be important tools in future studies on the molecular mechanisms by which environmental sensing is translated into regulation of strigolactone biosynthesis. As NSP1 and NSP2 are single copy genes in legumes, it implies that a single protein complex fulfills a dual regulatory function of different downstream targets; symbiotic and non-symbiotic, respectively.
2011-11-01 | GSE26548 | GEO
Project description:NSP1 is a major shutoff factor of the SARS-CoV-2 coronavirus, which is responsible for the COVID-19 pandemic. The functions of NSP1 and its contribution to SARS-CoV-2 propagation is not well understood. We tackled these questions utilizing methods such as RNA sequencing, ribosome profiling, and SLAMseq.
2022-04-10 | GSE200422 | GEO
Project description:Nitrosospira sp. 1 Nsp1 genome sequencing
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Project description:H3K9 acetylation and di-methylation changes in HL-60 cells following treatment with different compounds
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