Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Quantitative proteomic analysis identifies the unfolded protein response as a host pathway co-opted by ASFV to promote replication

ABSTRACT: African swine fever virus (ASFV) has caused severe consequences for the global pig industry. In this study, we conducted a multi-organ proteomic analysis using a 4D label-free quantitative proteomics approach and mapped the organ-specific proteomic landscape during ASFV infection. This work overcomes the limitations of most existing studies, which are primarily restricted to in vitro cell models, and providesprovide a more comprehensive understanding of ASFV infection and pathogenesis. Notably, the viral D117L protein is identified as a critical modulator of host cellular responses, directly subverting the unfolded protein response (UPR) pathway through specific interactions with host UPR-associated proteins. Collectively, our work lays the foundation for understanding the pathogenesis of ASFV, providing potential therapeutic strategies against African swine fever (ASF).

INSTRUMENT(S):

ORGANISM(S): Sus Scrofa Domesticus (domestic Pig)

TISSUE(S): Spleen, Lymph Node, Kidney

SUBMITTER: baohong Liu

LAB HEAD: Haixue Zheng

PROVIDER: PXD047161 | Pride | 2025-11-28

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	FA254LQ_PA244_5_Slot2-34_1_1643.d.zip	Other
	FA254LQ_PA246_3_Slot2-31_1_1639.d.zip	Other
	FA254LQ_PA248_0_Slot2-28_1_1635.d.zip	Other
	FA254LQ_PA249_0_Slot2-29_1_1636.d.zip	Other
	FA254LQ_PA250_3_Slot2-32_1_1640.d.zip	Other

Items per page:

1 - 5 of 39

Similar Datasets

ASFV array analysis

Project description:African swine fever virus (ASFV) produces a fatal acute hemorrhagic fever in domesticated pigs that potentially is a worldwide economic threat. Using an expressed sequence tag (EST) library-based antisense method of random gene inactivation and a phenotypic screen for limitation of ASFV replication in cultured human cells, we identified six host genes whose cellular functions are required by ASFV. These included three loci, BAT3 (HLA-B-associated transcript 3), C1qTNF (C1q and tumor necrosis factor-related protein 6), and TOM40 (translocase of outer mitochondrial membrane 40), for which antisense expression from a tetracycline-regulated promoter resulted in reversible inhibition of ASFV production by >99%. The effects of antisense transcription of the BAT3 EST and also of expression in the sense orientation of this EST, which encodes amino acid residues 450 to 518 of the mature BAT3 protein, were investigated more extensively. Sense expression of the BAT3 peptide, which appears to reversibly interfere with BAT3 function by a dominant negative mechanism, resulted in decreased synthesis of viral DNA and proteins early after ASFV infection, altered transcription of apoptosis-related genes as determined by cDNA microarray analysis, and increased cellular sensitivity to staurosporine-induced apoptosis. Antisense transcription of BAT3 reduced ASFV production without affecting abundance of the virus macromolecules we assayed. Our results, which demonstrate the utility of EST-based functional screens for the detection of host genes exploited by pathogenic viruses, reveal a novel collection of cellular genes previously not known to be required for ASFV infection. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed

2007-08-09 | E-GEOD-7581 | biostudies-arrayexpress

Porcine macrophages: ASFV-infected vs. mock-infected

Project description:Transcriptional profiling of porcine macrophages infected with Afraican swine fever virus (ASFV) infected cells and mock infection was conducted in this experiment.

2019-09-30 | GSE132905 | GEO

Transcription profiling of cultured human cells infected with African Swine Fever Virus (ASFV) to identify host genes required for replication of ASFV

2006-12-10 | E-SMDB-3898 | biostudies-arrayexpress

ASFV array analysis

2007-08-09 | GSE7581 | GEO

Structural and Functional Analysis of ASFV pI73R Reveals GNB1 Binding and Host Gene Modulation

Project description:African swine fever virus (ASFV) causes a highly fatal disease in domestic pigs, resulting in substantial economic losses to the global swine industry. Vaccine development continues to be hindered by limited characterization of viral proteins and their functional redundancies. In this study, we employ combined experimental and computational approaches to characterize the ASFV pI73R protein, which contains a Z-DNA binding domain and plays a critical role in ASFV virulence and pathogenesis. We demonstrate that pI73R shares significant structural similarity with transcription factors of the forkhead box (FOX) protein family. Overexpression of pI73R results in downregulation of CRNKL1, a core spliceosome component, suggesting a potential mechanism by which pI73R modulates host protein synthesis. Using high-resolution mass spectrometry, we map the pI73R interactome and identify the host protein GNB1 as a novel direct interactor of pI73R which may facilitate its nuclear transport. Furthermore, we show that pI73R exhibits consistent oligomerization and expression across different ASFV genotypes, highlighting its functional importance. Taken together, these results provide new insights into pI73R function, ASFV-host dynamics, and offer promising directions for antiviral strategy development.

2026-01-05 | PXD066360 | Pride

Transcriptome profiling in swine macrophages infected with African swine fever virus at single-cell resolution

Project description:African swine fever virus (ASFV) is the causative agent of African swine fever, a highly contagious and usually fatal disease in pigs. The pathogenesis of ASFV infection has not been clearly elucidated. Here, we used single-cell RNA-sequencing technology to survey the transcriptomic landscape of ASFV-infected primary porcine alveolar macrophages. The temporal dynamic analysis of viral genes revealed increased expression of viral transmembrane genes. Molecular characteristics in the ASFV-exposed cells exhibited the activation of antiviral signaling pathways with increased expression levels of interferon-stimulated genes and inflammatory- and cytokine-related genes. By comparing infected cells with unexposed cells, we showed that the unfolded protein response (UPR) pathway was activated in low viral load cells, while the expression level of UPR-related genes in high viral load cells was less than that in unexposed cells. Cells infected with various viral loads showed signature transcriptomic changes at the median progression of infection. Within the infected cells, differential expression analysis and coregulated virus–host analysis both demonstrated ASFV promoted metabolic pathways but inhibited interferon and UPR signaling, implying the regulation pathway of viral replication in host cells. Furthermore, our results revealed that the cell apoptosis pathway was activated upon ASFV infection. Mechanistically, the production of tumor necrosis factor alpha (TNF-α) induced by ASFV infection is necessary for cell apoptosis, highlighting the importance of TNF-α in ASFV pathogenesis. Collectively, the data provide insights into the comprehensive host responses and complex virus–host interactions during ASFV infection, which may instruct future research on antiviral strategies.

2022-04-05 | GSE168113 | GEO

EP152R-Mediated Endoplasmic Reticulum Stress Contributes to African Swine Fever Virus Infection via the PERK-eIF2α Pathway

Project description:African swine fever virus (ASFV) is a large, icosahedral, double-stranded DNA virus in the Asfarviridae family and the causative agent of African swine fever (ASF). ASFV causes a hemorrhagic fever with high mortality rates in domestic and wild pigs. ASFV contains an open reading frame named EP152R, previous research has shown that EP152R is an essential gene for virusrescue in swine macrophages. However, the detailed functions of ASFV EP152R remain elusive. Herein, we demonstrate that EP152R, a membrane protein located in the endoplasmic reticulum (ER), induces ER stress and swelling, triggering the PERK/eIF2α pathway and broadly inhibiting host protein synthesis in vitro. Additionally, EP152R strongly promotes immune evasion, reduces cell proliferation, and alters cellular metabolism. These results suggest that ASFV EP152R plays a critical role in the intracellular environment, facilitating viral replication. Furthermore, virus-level experiments have shown that the knockdown of EP152R or PERK inhibitors efficiently affects viral replication by decreasing viral gene expression. In summary, these findings reveal a series of novel functions of ASFV EP152R and have important implications for understanding host-pathogen interactions.

2024-08-22 | GSE275101 | GEO

RNA-seq of early responses to ASFV

Project description:In this project we would like to study immune responses to African swine fever virus in pigs. We have realized a large animal experiment using two different viruses and pigs with different immune status. We have collected paxgene blood RNA tubes in order to investigate transcriptional changes at different stages of the early immune response.

2022-07-06 | E-MTAB-11634 | biostudies-arrayexpress

Expression profiles of long noncoding RNAs and mRNAs in primary porcine macrophages (PAMs) Infected with African swine fever virus

Project description:Long noncoding RNAs (lncRNAs) participate in regulating many biological processes. However, their roles in African swine fever virus(ASFV) pathogenicity are largely unknown. Here, we analyzed the expression profile of lncRNAs and mRNAs in the ASFV-infected or uninfected PAMs by high-throughput sequencing

2024-07-27 | GSE180939 | GEO

Insights into the role of VPS39 and its interaction with CP204L and A137R in ASFV infection

Project description:The African swine fever virus (ASFV) is a large and complex DNA virus that causes a highly le-thal disease in swine, for which no antiviral drugs or vaccines are currently available. Studying viral–host protein-protein interactions advances our understanding of the molecular mecha-nisms underlying viral replication and pathogenesis and can facilitate the discovery of antiviral therapeutics. In this study, we employed affinity tagging and purification mass spectrometry to characterize the interactome of VPS39, an important cellular factor during the early phase of ASFV replication. The interaction network of VPS39 revealed associations with mitochondrial proteins involved in membrane contact sites formation and cellular respiration. We show that ASFV proteins CP204L and A137R target VPS39 by interacting with its clathrin heavy chain func-tional domain. Furthermore, we elaborate on the potential mechanisms by which VPS39 may contribute to ASFV replication and prioritize interactions for further investigation into mito-chondrial protein function in the context of ASFV infection.

2024-09-17 | PXD054169 | Pride