State Key Laboratories of Agrobiotechnology, Department of Microbiology and Immunology, College of Biological Science, China Agricultural University, Beijing, 100193, China.
Virol J. 2012 Aug 21;9:165. doi: 10.1186/1743-422X-9-165.
Porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failure and respiratory illness in pigs and usually establishes a persistent infection. Previous studies suggested that interleukin-10 (IL-10) could play a critical role in PRRSV-induced immunosuppression. However, the ability of PRRSV to induce IL-10 in infected cells is controversial. In this study, we further investigated this issue using PRRSV strain CH-1a, which is the first North American genotype strain isolated in China.
PRRSV strain CH-1a could significantly up-regulate IL-10 production both at mRNA and protein levels in porcine alveolar macrophages (PAMs), bone marrow-derived macrophages (BMDMs), and monocyte-derived macrophages (MDMs). However, up-regulation of IL-10 by PRRSV was retarded by specific inhibitors of p38 mitogen-activated protein kinase (MAPK) (SB203580) and NF-κB (BAY11-7082). Additionally, p38 MAPK and NF-κB pathways but not ERK1/2 MAPK were actually activated in PRRSV-infected BMDMs as demonstrated by western blot analysis, suggesting that p38 MAPK and NF-κB pathways are involved in the induction of IL-10 by PRRSV infection. Transfection of PAMs and PAM cell line 3D4/21 (CRL-2843) with viral structural genes showed that glycoprotein5 (GP5) could significantly up-regulate IL-10 production, which was dependent on p38 MAPK and signal transducer and activator of transcription-3 (STAT3) activation. We also demonstrated that a full-length glycoprotein was essential for GP5 to induce IL-10 production.
PRRSV strain CH-1a could significantly up-regulate IL-10 production through p38 MAPK activation.
猪繁殖与呼吸综合征病毒（PRRSV）可导致猪繁殖失败和呼吸道疾病，通常建立持续性感染。先前的研究表明，白细胞介素-10（IL-10）在 PRRSV 诱导的免疫抑制中可能发挥关键作用。然而，PRRSV 在感染细胞中诱导 IL-10 的能力存在争议。在这项研究中，我们使用 PRRSV 株 CH-1a 进一步研究了这个问题，CH-1a 是在中国分离的第一个北美基因型株。
PRRSV 株 CH-1a 可显著上调猪肺泡巨噬细胞（PAMs）、骨髓来源巨噬细胞（BMDMs）和单核细胞来源巨噬细胞（MDMs）中 IL-10 的 mRNA 和蛋白水平。然而，p38 丝裂原活化蛋白激酶（MAPK）（SB203580）和 NF-κB（BAY11-7082）的特异性抑制剂可延迟 PRRSV 对 IL-10 的上调。此外，Western blot 分析表明，PRRSV 感染的 BMDMs 中 p38 MAPK 和 NF-κB 途径而非 ERK1/2 MAPK 实际上被激活，表明 p38 MAPK 和 NF-κB 途径参与 PRRSV 感染诱导的 IL-10 诱导。用病毒结构基因转染 PAMs 和 PAM 细胞系 3D4/21（CRL-2843）表明，糖蛋白 5（GP5）可显著上调 IL-10 的产生，这依赖于 p38 MAPK 和信号转导和转录激活因子 3（STAT3）的激活。我们还证明，全长糖蛋白对于 GP5 诱导 IL-10 的产生是必需的。
PRRSV 株 CH-1a 可通过 p38 MAPK 激活显著上调 IL-10 的产生。
