Guanylate-binding protein 2 orchestrates innate immune responses against murine norovirus and is antagonized by the viral protein NS7

Yu, Peifa; Li, Yang; Li, Yunlong; Miao, Zhijiang; Peppelenbosch, Maikel P.

doi:10.1074/jbc.ra120.013544

Cited by 24 publications

(26 citation statements)

References 50 publications

(77 reference statements)

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“…The pathway enrichment analysis was performed with up and down regulated genes. Enriched genes such as KMO (kynurenine 3-monooxygenase) [ Swainson et al, 2019 ], KYNU (kynureninase) [ Finney et al, 2019 ], BIRC3 [ Rouka, 2018 ], GBP2 [ Yu et al, 2020 ], DDX58 [ Zhu et al, 2019 ], IRF8 [ Sun et al, 2016 ], IFIT2 [ Butchi et al, 2014 ], TRIM5 [ van Manen et al, 2008 ], RSAD2 [ Kurokawa et al, 2019 ], IFI6 [ Richardson et al, 2018 ], SP100 [ Kim et al, 2011 ], TRIM21 [ Fan et al, 2016 ], CXCL9 [ Huang et al, 2012 ], CCL8 [ Rom et al, 2010 ], CXCL11 [ Chalin et al, 2019 ], ELMO1 [ Janardhan et al, 2004 ], ITK (IL2 inducible T cell kinase) [ He et al, 2014 ], CYP27A1 [ Yang et al, 2019 ], RPS13 [ Robichaux et al, 2016 ], RPS17 [ Kenney and Meng, 2015 ], RPS19 [ Ganaie et al, 2014 ], RPL4 [ Chen et al, 2016 ], RPL13 [ Han et al, 2020 ], RPL18 [ R. Wang et al, 2018 ], RUVBL2 [ Morwitzer et al, 2019 ], JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [ Benn et al, 1996 ] and GPX4 [ Brault et al, 2016 ] were involved in development of different viral infections, but these genes may be responsible for progression of SARS-CoV-2 infection. Enriched genes such as IDO1 [ Fox et al, 2015 ], CCL2 [ Lai et al, 2017 ], AIM2 [ Zhang et al, 2017 ], STAT2 [ Warnking et al, 2015 ], GBP5 [ Feng et al, 2017 ], CASP1 [ Ren et al, 2017 ], OAS2 [ Zhao et al, 2019 ], STAT4 [ Bot et al, 2003 ], TRIM22 [ Di Pietro et al, 2013 ], PML (promyelocyticleukemia) [ Li et al, 2009 ], IFITM1 [ Yu et al, 2015 ], ISG15 [ Sanyal et al, 2013 ], MX1 [ Verhelst et al, 2012 ], MX2 [ Jin et al, 2001 ], IRF4 [ Ainsua-Enrich et al, 2019 ], NEDD4 [ Lin et al, 2020 ], HERC5 [ Tang et al, 2010 ]...…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analyses of significant genes, related pathways, and candidate diagnostic biomarkers and molecular targets in SARS-CoV-2/COVID-19

Vastrad¹,

Vastrad²,

Tengli

2020

Gene Reports

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Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection is a leading cause of pneumonia and death. The aim of this investigation is to identify the key genes in SARS-CoV-2 infection and uncover their potential functions. We downloaded the expression profiling by high throughput sequencing of GSE152075 from the Gene Expression Omnibus database. Normalization of the data from primary SARS-CoV-2 infected samples and negative control samples in the database was conducted using R software. Then, joint analysis of the data was performed. Pathway and Gene ontology (GO) enrichment analyses were performed, and the protein-protein interaction (PPI) network, target gene - miRNA regulatory network, target gene - TF regulatory network of the differentially expressed genes (DEGs) were constructed using Cytoscape software. Identification of diagnostic biomarkers was conducted using receiver operating characteristic (ROC) curve analysis. 994 DEGs (496 up regulated and 498 down regulated genes) were identified. Pathway and GO enrichment analysis showed up and down regulated genes mainly enriched in the NOD-like receptor signaling pathway, Ribosome, response to external biotic stimulus and viral transcription in SARS-CoV-2 infection. Down and up regulated genes were selected to establish the PPI network, modules, target gene - miRNA regulatory network, target gene - TF regulatory network revealed that these genes were involved in adaptive immune system, fluid shear stress and atherosclerosis, influenza A and protein processing in endoplasmic reticulum. In total, ten genes (CBL, ISG15, NEDD4, PML, REL, CTNNB1, ERBB2, JUN, RPS8 and STUB1) were identified as good diagnostic biomarkers. In conclusion, the identified DEGs, hub genes and target genes contribute to the understanding of the molecular mechanisms underlying the advancement of SARS-CoV-2 infection and they may be used as diagnostic and molecular targets for the treatment of patients with SARS-CoV-2 infection in the future.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analyses of significant genes, related pathways, and candidate diagnostic biomarkers and molecular targets in SARS-CoV-2/COVID-19

Vastrad¹,

Vastrad²,

Tengli

2020

Gene Reports

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“…These studies thus revealed the broad antiviral potential of GBPs. Ever since, GBP-mediated restriction of viral replication has been observed in several mammalian hosts (human, mouse, pig, tree shrew) for different virus classes represented by dengue virus, murine novo virus, classical swine fever virus, and Herpes simplex virus [3,[118][119][120][121]. However, the mechanisms underlying GBPs' broad antiviral activity remain poorly understood.…”

Section: Gbps Promote Antiviral Activities Against a Broad Range Of Vmentioning

confidence: 99%

Human guanylate binding proteins: nanomachines orchestrating host defense

Kutsch

Coers

2021

The FEBS Journal

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The ability of any single cell of our body to defend itself against intracellular pathogens is a critical aspect of the human immune system. Many of our cells’ intrinsic defenses are orchestrated by a set of guanylate binding proteins (GBPs). Here, we synthesize recent studies to generate a comprehensive model for the biochemical and cell biological mechanisms by which GBPs defend against protozoan, bacterial, and viral pathogens.

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“…Human GBPs share a high degree of sequence homology and carry a conserved N-terminal globular GTPase domain followed by a C-terminal helical domain. GTPase activity is required for the antimicrobial activity of GBPs (5–7) and allows GBP dimerization and polymerization (8–10). GTP hydrolysis is well conserved between GBPs.…”

Section: Introductionmentioning

confidence: 99%

Bacterial factors drive the differential targeting of Guanylate Binding Proteins toFrancisellaandShigella

Michal²,

Degabriel³

et al. 2021

Preprint

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Guanylate-Binding Proteins (GBPs) are interferon-inducible GTPases that play a key role in cell autonomous responses against intracellular pathogens. Seven GBPs are present in humans. Despite sharing high sequence similarity, subtle differences among GBPs translate into functional divergences that are still largely not understood. A key step for the antimicrobial activity of GBPs towards cytosolic bacteria is the formation of supramolecular GBP complexes on the bacterial surface. Such complexes are formed when GBP1 binds lipopolysaccharide (LPS) from Shigella and Salmonella and further recruits GBP2, 3, and 4. Here, we investigated GBPs recruitment on Francisella novicida, a professional cytosol-dwelling pathogen with an atypical tetra-acylated LPS. Co-infection experiments demonstrated that GBPs target preferentially S. flexneri compared to F. novicida. F. novicida was coated by GBP1 and GBP2 in human macrophages but escaped targeting by GBP3 and GBP4. GBP1 and GBP2 features that drive recruitment to F. novicida were investigated revealing that GBP1 GDPase activity is required to initiate GBP recruitment to F. novicida but facultative to target S. flexneri. Furthermore, analysis of chimeric GBP2/5 proteins identified a central domain in GBP2 necessary and sufficient to target F. novicida. Finally, a F. novicida ΔlpxF mutant with a penta-acylated lipid A was targeted by GBP3 suggesting that lipid A tetra-acylation contributes to escape from GBP3. Altogether our results indicate that GBPs have different affinity for different bacteria and that the repertoire of GBPs recruited onto cytosolic bacteria is dictated by GBP-intrinsic features and specific bacterial factors, including the structure of the lipid A.

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Guanylate-binding protein 2 orchestrates innate immune responses against murine norovirus and is antagonized by the viral protein NS7

Cited by 24 publications

References 50 publications

Bioinformatics analyses of significant genes, related pathways, and candidate diagnostic biomarkers and molecular targets in SARS-CoV-2/COVID-19

Bioinformatics analyses of significant genes, related pathways, and candidate diagnostic biomarkers and molecular targets in SARS-CoV-2/COVID-19

Human guanylate binding proteins: nanomachines orchestrating host defense

Bacterial factors drive the differential targeting of Guanylate Binding Proteins toFrancisellaandShigella

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