Liu Yihao, Du Yinping, Wang Honglei, Du Li, Feng Wen-Hai
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China; Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China; Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Virology. 2017 Jun;506:64-72. doi: 10.1016/j.virol.2017.03.009. Epub 2017 Mar 24.
The acute phase of respiratory distress caused by porcine reproductive and respiratory syndrome virus (PRRSV) is likely a consequence of the release of inflammatory cytokines in the lung. IL-8, the main chemokine and activator of neutrophils, might be related to the lung injury upon PRRSV infection. In this study, we showed that PRRSV induced IL-8 expression in vivo and in vitro. Subsequently, we demonstrated that JNK and NF-κB pathways were activated upon PRRSV infection and required for the enhancement of IL-8 expression. We further verified that PRRSV-activated TAK-1 was essential for the activation of JNK and NF-κB pathways and IL-8 expression. Moreover, we revealed an AP-1 binding motif in the cloned porcine IL-8 (pIL-8) promoter, and deletion of this motif abolished the pIL-8 promoter activity. Finally, we found that the JNK-activated AP-1 subunit c-Jun was critical for the up-regulation of IL-8 expression by PRRSV. These data suggest that PRRSV-induced IL-8 production is likely through the TAK-1/JNK/AP-1 pathways.
由猪繁殖与呼吸综合征病毒（PRRSV）引起的呼吸窘迫急性期可能是肺部炎症细胞因子释放的结果。白细胞介素8（IL-8）是主要的趋化因子和中性粒细胞激活剂，可能与PRRSV感染后的肺损伤有关。在本研究中，我们表明PRRSV在体内和体外均可诱导IL-8表达。随后，我们证明PRRSV感染后JNK和NF-κB信号通路被激活，且这两条信号通路是IL-8表达增强所必需的。我们进一步证实，PRRSV激活的TAK-1对于JNK和NF-κB信号通路的激活以及IL-8的表达至关重要。此外，我们在克隆的猪IL-8（pIL-8）启动子中发现了一个AP-1结合基序，删除该基序可消除pIL-8启动子活性。最后，我们发现JNK激活的AP-1亚基c-Jun对于PRRSV上调IL-8表达至关重要。这些数据表明，PRRSV诱导的IL-8产生可能是通过TAK-1/JNK/AP-1信号通路实现的。
