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The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted host antiviral signaling and translation

ABSTRACT: To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 SARS-CoV-2 viral proteins using proximity proteomics.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

SUBMITTER: Yen-Yu Yang

LAB HEAD: Yinsheng Wang

PROVIDER: PXD023239 | Pride | 2022-02-16

REPOSITORIES: Pride

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	SARS_Weili_1.raw	Raw
	SARS_Weili_10.raw	Raw
	SARS_Weili_11.raw	Raw
	SARS_Weili_12.raw	Raw
	SARS_Weili_13.raw	Raw

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The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation.

Meyers Jordan M JM Ramanathan Muthukumar M Shanderson Ronald L RL Beck Aimee A Donohue Laura L Ferguson Ian I Guo Margaret G MG Rao Deepti S DS Miao Weili W Reynolds David D Yang Xue X Zhao Yang Y Yang Yen-Yu YY Blish Catherine C Wang Yinsheng Y Khavari Paul A PA

PLoS pathogens 20211001 10

Viral proteins localize within subcellular compartments to subvert host machinery and promote pathogenesis. To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 SARS-CoV-2 viral proteins using proximity proteomics. This identified viral proteins at specific intracellular locations, such as association of accessary proteins with intracellular membranes, and projected SARS-CoV-2 impacts on innate immune signaling, ER-Golgi transport, and protein translation. It i ...[more]

PMID: 34597346

Similar Datasets

The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation.

Project description:Viral proteins localize within subcellular compartments to subvert host machinery and promote pathogenesis. To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 SARS-CoV-2 viral proteins using proximity proteomics. This identified viral proteins at specific intracellular locations, such as association of accessary proteins with intracellular membranes, and projected SARS-CoV-2 impacts on innate immune signaling, ER-Golgi transport, and protein translation. It identified viral protein adjacency to specific host proteins whose regulatory variants are linked to COVID-19 severity, including the TRIM4 interferon signaling regulator which was found proximal to the SARS-CoV-2 M protein. Viral NSP1 protein adjacency to the EIF3 complex was associated with inhibited host protein translation whereas ORF6 localization with MAVS was associated with inhibited RIG-I 2CARD-mediated IFNB1 promoter activation. Quantitative proteomics identified candidate host targets for the NSP5 protease, with specific functional cleavage sequences in host proteins CWC22 and FANCD2. This data resource identifies host factors proximal to viral proteins in living human cells and nominates pathogenic mechanisms employed by SARS-CoV-2.Author summarySARS-CoV-2 is the latest pathogenic coronavirus to emerge as a public health threat. We create a database of proximal host proteins to 17 SARS-CoV-2 viral proteins. We validate that NSP1 is proximal to the EIF3 translation initiation complex and is a potent inhibitor of translation. We also identify ORF6 antagonism of RNA-mediate innate immune signaling. We produce a database of potential host targets of the viral protease NSP5, and create a fluorescence-based assay to screen cleavage of peptide sequences. We believe that this data will be useful for identifying roles for many of the uncharacterized SARS-CoV-2 proteins and provide insights into the pathogenicity of new or emerging coronaviruses.

| S-EPMC7924263 | biostudies-literature

The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation.

| S-EPMC8513853 | biostudies-literature

The host targets of SARS-CoV-2 protein NSP5

Project description:To identity the host targets of the SARS-CoV-2 protease NSP5, SILAC-based quantitative proteomics was performed in comparing the binding partners of wildtype or catalytically-inactive C145A mutant.

2021-10-27 | PXD023277 | Pride

The PDZ-binding motif of SARS-CoV envelope protein is a determinant of viral pathogenesis

Project description:A recombinant SARS-CoV lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major virulence determinant in vivo. Elimination of SARS-CoV E protein PBM by using reverse genetics led to attenuated viruses (SARS-CoV-mutPBM) and to a reduction in the deleterious exacerbate immune response triggered during infection with the parental virus (SARS-CoV-wt). Cellular protein syntenin bound E protein PBM during SARS-CoV infection. Syntenin activates p38 MAPK leading to overexpression of inflammatory cytokines, and we have shown that active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM (SARS-CoV-mutPBM) as compared with the parental virus (SARS-CoV-wt), leading to a decreased expression of inflammatory cytokines and to viral attenuation. Therefore, E protein PBM is a virulence factor that activates pathogenic immune response most likely by using syntenin as a mediator of p38 MAPK induced inflammation. Three biological replicates were independently hybridized (one channel per slide) for each sample type (SARS-CoV-wt, SARS-CoV-mutPBM, Mock). Slides were Sure Print G3 Agilent 8x60K Mouse (G4852A-028005)

2014-10-31 | E-GEOD-52920 | biostudies-arrayexpress

An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the coronavirus disease-19 (COVID-19) pandemic, was identified in late 2019 and went on to cause over 3.3 million deaths in 15 months. To date, targeted antiviral interventions against COVID-19 are limited. The spectrum of SARS-CoV-2 infection ranges from asymptomatic to fatal disease. However, the reasons for varying outcomes to SARS-CoV-2 infection are yet to be elucidated. Here we show that an endogenously activated interferon lambda (IFNλ) pathway leads to resistance against SARS-CoV-2 infection. Using a well-differentiated primary nasal epithelial cell (WD-PNEC) model from multiple adult donors, we discovered that susceptibility to SARS-CoV-2 infection, but not respiratory syncytial virus (RSV) infection, varied. One of four donors was resistant to SARS-CoV-2 infection. High baseline IFNλ expression levels and associated interferon stimulated genes correlated with resistance to SARS-CoV-2 infection. Inhibition of the JAK/STAT pathway in WD-PNECs with high endogenous IFNλ secretion resulted in higher SARS-CoV-2 titres. Conversely, prophylactic IFNλ treatment of WD-PNECs susceptible to infection resulted in reduced viral titres. An endogenously activated IFNλ response, possibly due to genetic differences, may be one explanation for the differences in susceptibility to SARS-CoV-2 infection in humans.

2022-04-05 | GSE199743 | GEO

Bulk RNA Barcoding and sequencing (BRB-seq) of Mock, SARS-CoV, and SARS-CoV-2 infected human airway epithelial cell cultures at 33°C and 37°C

Project description:For the assessment of host response dynamics to SARS-CoV and SARS-CoV-2 infections in human airway epithelial cells at ambient temperature corresponding to the upper or lower respiratory tract. We performed a temporal transcriptome analysis on human airway epithelial cell (hAEC) cultures infected with SARS-CoV and SARS-CoV-2, as well as uninfected hAEC cultures, incubated either at 33°C or 37°C. hAEC cultures were harvested at 24, 48 72, 96 hpi and processed for Bulk RNA Barcoding and sequencing (BRB-seq), which allows a rapid and sensitive genome-wide transcriptomic analysis in a highly multiplexed manner. Transcriptome data was obtained from a total of 7 biological donors for pairwise comparisons of SARS-CoV or SARS-CoV-2 virus-infected to unexposed hAEC cultures at respective time points and temperatures.

2020-11-27 | E-MTAB-9781 | biostudies-arrayexpress

Characterization of ACTN4 as a novel antiviral target against SARS-CoV-2

Project description:this study unveil the pivotal role of ACTN4 in SARS-CoV-2 infection, offering novel insights into the intricate interplay between the virus and host cells, and reveal two potential candidates for future anti SARS-CoV-2 drug development.

2024-08-14 | GSE274550 | GEO

Absence of host innate immune responses in SARS-CoV-infected ferrets upon subsequent challenge

Project description:To further investigate the underlying mechanisms of severe acute respiratory syndrome (SARS) pathogenesis and evaluate the therapeutic efficacy of potential drugs and vaccines it is necessary to use an animal model that is highly representative of the human condition in terms of respiratory anatomy, physiology and clinical sequelae. The ferret, Mustela putorius furo, supports SARS-CoV replication and displays many of the symptoms and pathological features seen in SARS-CoV-infected humans. We have recently established a SARS-CoV infection-challenge ferret platform for use in evaluating potential therapeutics to treat SARS. The main objective of the current study was to extend our previous results and identify early host immune responses upon infection and determine immune correlates of protection upon challenge with SARS-CoV in ferrets. Keywords: time course This study is a simple time course (58 day) examination of host responses in 35 SARS-CoV (TOR2) infected ferrets with the addition of a challenge inoculation of SARS CoV (TOR2) at day 29 post infection. Three mock-infected ferrets are included as negative controls. Due to the unavailability of ferret microarrays, Affymetrix Canine 2.0 oligonucleotide arrays were chosen following sequence analysis of our ferret cDNA library (~5000 clones) and demonstration of high levels of homology (>80%) between dog and ferret.

2013-05-28 | E-GEOD-11704 | biostudies-arrayexpress

Gut microbiota interplay with COVID-19 reveals links to host lipid metabolism among Middle Eastern populations

Project description:We discovered an enrichment of linoleic acid, ether lipid, glycerolipid, and glycerophospholipid metabolism among the SARS-CoV-2 infected group, suggesting a link to SARS-CoV-2 entry and replication in host cells.The identified differences provide a new insight to enrich our understanding of SARS-CoV-2-related changes in gut microbiota, their metabolic capabilities, and potential screening biomarkers linked to COVID-19 disease severity.

2021-11-30 | GSE185406 | GEO

Pseudoknot RNA degraders – directed and irreversible degradation of SARS-CoV-2 genome as an antiviral strategy

Project description:We demonstrate that the pseudoknot binder MTDB selectively degrades coronaviral pseudoknots in vitro, in cells and in a SARS-CoV-2 infection mouse model, which means it has great potential to be used as an anti-SARS-CoV-2 therapeutic.

2024-08-06 | GSE182826 | GEO

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