8887cf7f5ffe0082e2cb6c37569ee392 pmc_11860178.pdf ed609d802a84154456542f24428e48e23763146a pmc_11860178.pdf 7f9871a9d2546e92955833c61ab81b0cb921d9f01aadf06c56684d2c00e03287 pmc_11860178.pdf Title: Gene Expression Signatures of Porcine Bone Marrow-Derived Antigen-Presenting Cells Infected with Classical Swine Fever Virus Subject: For a better understanding of classical swine fever (CSF) pathogenesis, a transcriptomic analysis was performed using porcine bone marrow (BM)-derived antigen-presenting cells (APCs) infected ex vivo with two different cDNA-derived classical swine fever virus (CSFV) strains, the low-virulence Pinar de Rio (vPdR-36U) or the lethal vPdR-H30K-5U. The transcriptomic profile of vPdR-36U- or vPdR-H30K-5U-infected versus noninfected cells revealed 946 and 2643 differentially expressed genes (DEGs), respectively. The upregulation of ISG15, CXCL-10, ADAM8, and CSF1 was found after infection with vPdR-36U, which could contribute to the generation of mild CSF forms. In contrast, cells infected with the lethal vPdR-H30K-5U overexpressed the immune checkpoint molecules PD-L1, CD276, and LAG3, which are involved in T-cell exhaustion and could be associated with adaptive immunity impairment. vPdR-H30K-5U also induced increased expression of PPBP, IL-8, IL-6, ECE1, and Rab27b, which are mediators of inflammatory responses that can be involved in cytokine storms. The TNF signaling pathway, which is related to the activation and proliferation of different subsets of immune cells, including CD4+ T cells, was notably upregulated in response to the low-pathogenicity virus. The Th17, Th1, and Th2 differentiation pathways were downregulated by the highly pathogenic virus only, supporting the role of T-cell-mediated immunity in protecting against CSFV. Keywords: classical swine fever virus; bone marrow-derived antigen-presenting cells; transcriptomic profile; disease severity; differentially expressed genes Author: Liani Coronado, Miaomiao Wang, Jose Alejandro Bohórquez, Adriana Muñoz-Aguilera, Mònica Alberch, Patricia Martínez, Nicolas Ruggli, Yuliaxis Ramayo-Caldas and Llilianne Ganges Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Jan 24 09:42:08 2025 CET ModDate: Fri Jan 24 09:48:45 2025 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 5999455 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WLFTRW+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 ZHNHUX+URWPalladioL-Roma Type 1 Custom yes yes yes 16 0 UXDUPA+URWPalladioL-Bold Type 1 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FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Cells and Viruses Destination: subsection.2.1 Item: Title: BMHC Culture and CSFV Infection Destination: subsection.2.2 Item: Title: RNA-Seq Destination: subsection.2.3 Item: Title: Bioinformatic and Statistical Analyses Destination: subsection.2.4 Item: Title: Validation of RNA-Seq Data Destination: subsection.2.5 Item: Title: Results Destination: section.3 Children: Item: Title: Similar Infection Levels with CSFV vPdR-36U or vPdR-H30K-5U in Porcine BM-APCs Destination: subsection.3.1 Item: Title: Gene Expression Patterns in Porcine BM-APCs After Infection with CSFV Destination: subsection.3.2 Item: Title: The Capacity of CSFV to Modulate Immune, Antiviral, Cell Cycle, and Metabolic Pathways Depends on the Degree of Viral Virulence Destination: subsection.3.3 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: appendix.A. Info: Title: Gene Expression Signatures of Porcine Bone Marrow-Derived Antigen-Presenting Cells Infected with Classical Swine Fever Virus Author: Liani Coronado, Miaomiao Wang, Jose Alejandro Bohórquez, Adriana Muñoz-Aguilera, Mònica Alberch, Patricia Martínez, Nicolas Ruggli, Yuliaxis Ramayo-Caldas and Llilianne Ganges Subject: For a better understanding of classical swine fever (CSF) pathogenesis, a transcriptomic analysis was performed using porcine bone marrow (BM)-derived antigen-presenting cells (APCs) infected ex vivo with two different cDNA-derived classical swine fever virus (CSFV) strains, the low-virulence Pinar de Rio (vPdR-36U) or the lethal vPdR-H30K-5U. The transcriptomic profile of vPdR-36U- or vPdR-H30K-5U-infected versus noninfected cells revealed 946 and 2643 differentially expressed genes (DEGs), respectively. The upregulation of ISG15, CXCL-10, ADAM8, and CSF1 was found after infection with vPdR-36U, which could contribute to the generation of mild CSF forms. In contrast, cells infected with the lethal vPdR-H30K-5U overexpressed the immune checkpoint molecules PD-L1, CD276, and LAG3, which are involved in T-cell exhaustion and could be associated with adaptive immunity impairment. vPdR-H30K-5U also induced increased expression of PPBP, IL-8, IL-6, ECE1, and Rab27b, which are mediators of inflammatory responses that can be involved in cytokine storms. The TNF signaling pathway, which is related to the activation and proliferation of different subsets of immune cells, including CD4+ T cells, was notably upregulated in response to the low-pathogenicity virus. The Th17, Th1, and Th2 differentiation pathways were downregulated by the highly pathogenic virus only, supporting the role of T-cell-mediated immunity in protecting against CSFV. 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