Project description:African swine fever virus is highly contagious and causes a fatal infectious disease in pigs, resulting in a significant global impact on pork supply. The African swine fever virus RNA polymerase serves as a crucial multifunctional protein complex responsible for genome transcription and regulation. Therefore, it is essential to investigate its structural and functional characteristics for the prevention and control of African swine fever. Here, we determine the structures of endogenous African swine fever virus RNA polymerase in both nucleic acid-free and elongation states. The African swine fever virus RNA polymerase shares similarities with the core of typical RNA polymerases, but possesses a distinct subunit M1249L. Notably, the dynamic binding mode of M1249L with RNA polymerase, along with the C-terminal tail insertion of M1249L in the active center of DNA-RNA scaffold binding, suggests the potential of M1249L to regulate RNA polymerase activity within cells. These results are important for understanding the transcription cycle of African swine fever virus and for developing antiviral strategies.
Project description:Purpose: This goal of this study was to explore the host transcriptomic responses in African swine fever virus experimentally infected pigs using RNA-Sequencing. Methods: RNAs acquired from ten different organ tissue samples were sequenced. Sequencing reads were preprocessed, aligned with the reference genome, assembled and expressions were estimated through bioinformatics approaches. Result: Several uprugulated DEGs were identified. Conclusion: We found important candidate genes and pathways for further testing in African swine fever virus infection in pig.
Project description:African swine fever (ASF) is the most dangerous disease of pigs and causes enormous economic losses in the global pig industry. However, the mechanism of ASF virus (ASFV) infection is unclear. Hence, we wanted to understand the host response mechanism upon ASFV infection. We analyzed the differentially expressed proteins (DEPs) between ASFV-infected and un-infected serum samples using quantitative proteomics. Setting the p-value < 0.05 and |log2 (fold change)| > 1.5, we identified 173 DEPs, including 57 upregulated and 116 downregulated proteins, which belonged to various biological processes and pathways according to the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The enriched pathways include the immune system, metabolism, and inflammation.
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.
Project description:Quantitiative analysis of proteomes of porcine macrophages and the stable cell line WSL infected with African swine fever virus using a nanoLC MALDI-Tof/Tof MS platform.
The impact of the infection on the two cell types was analyzed using Gene Ontology term and KEGG pathway enrichment analysis.
