Abstract:
The pathogenesis of porcine circovirus type 2b (PCV2b) and swine influenza A virus (SwIV) during co-infection in swine respiratory cells is poorly understood. To elucidate the impact of PCV2b/SwIV co-infection, newborn porcine tracheal epithelial cells (NPTr) and immortalized porcine alveolar macrophages (iPAM 3D4/21) were co-infected with PCV2b and SwIV (H1N1 or H3N2 genotype). Viral replication, cell viability and cytokine mRNA expression were determined and compared between single-infected and co-infected cells. Finally, 3\'mRNA sequencing was performed to identify the modulation of gene expression and cellular pathways in co-infected cells. It was found that PCV2b significantly decreased or improved SwIV replication in co-infected NPTr and iPAM 3D4/21 cells, respectively, compared to single-infected cells. Interestingly, PCV2b/SwIV co-infection synergistically up-regulated IFN expression in NPTr cells, whereas in iPAM 3D4/21 cells, PCV2b impaired the SwIV IFN induced response, both correlating with SwIV replication modulation. RNA-sequencing analyses revealed that the modulation of gene expression and enriched cellular pathways during PCV2b/SwIV H1N1 co-infection is regulated in a cell-type-dependent manner. This study revealed different outcomes of PCV2b/SwIV co-infection in porcine epithelial cells and macrophages and provides new insights on porcine viral co-infections pathogenesis.
摘要:
猪圆环病毒2b型(PCV2b)和猪甲型流感病毒(SwIV)在猪呼吸道细胞共感染期间的发病机理知之甚少。为了阐明PCV2b/SwIV共感染的影响,新生猪气管上皮细胞(NPTr)和永生化猪肺泡巨噬细胞(iPAM3D4/21)与PCV2b和SwIV(H1N1或H3N2基因型)共感染。病毒复制,在单次感染和共感染的细胞之间测定并比较细胞活力和细胞因子mRNA表达。最后,进行3mRNA测序以鉴定共感染细胞中基因表达和细胞途径的调节。发现PCV2b在共感染的NPTr和iPAM3D4/21细胞中显著降低或改善SwIV复制,分别,与单一感染的细胞相比。有趣的是,PCV2b/SwIV共感染协同上调NPTr细胞中的IFN表达,而在iPAM3D4/21细胞中,PCV2b损害了SwIVIFN诱导的反应,两者都与SwIV复制调节相关。RNA测序分析显示,在PCV2b/SwIVH1N1共感染期间,基因表达和富集的细胞途径的调节以细胞类型依赖性方式进行调节。这项研究揭示了猪上皮细胞和巨噬细胞中PCV2b/SwIV共感染的不同结果,并为猪病毒共感染的发病机理提供了新的见解。