College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.
J Virol. 2022 Apr 13;96(7):e0000322. doi: 10.1128/jvi.00003-22. Epub 2022 Mar 16.
MicroRNAs (miRNAs) play an important role in the virus-host interaction. Our previous work has indicated that the expression level of miR-10a increased in porcine alveolar macrophages (PAMs) during porcine reproductive and respiratory syndrome virus (PRRSV) infection and further inhibited viral replication through downregulates the expression of host molecule signal-recognition particle 14 (SRP14) protein. However, the molecular mechanism of miR-10a increased after PRRSV infection remains unknown. In the present study, transcription factor interferon regulatory factor 8 (IRF8) was identified as a negative regulator of miR-10a. PRRSV infection decreases the expression level of IRF8 in PAMs, leading to upregulating miR-10a expression to play an anti-PRRSV role. Meanwhile, this work first proved that IRF8 promoted PRRSV replication in an miR-10a-dependent manner. Further, we explained that SRP14, the target gene of miR-10a, promotes the synthesis of the PRRSV genome by interacting with the viral components Nsp2, thus facilitating PRRSV replication. In conclusion, we identified a novel IRF8-miR-10a-SRP14 regulatory pathway against PRRSV infection, which provides new insights into virus-host interactions and suggests potential new antiviral strategies to control PRRSV. Porcine reproductive and respiratory syndrome virus (PRRSV) has rapidly spread to the global pig industry and caused incalculable economic damage since first discovered in the 1980s. However, conventional vaccines do not provide satisfactory protection. Understanding the molecular mechanisms of host resistance to PRRSV infection is necessary to develop safe and effective strategies to control PRRSV. During viral infection, miRNAs play vital roles in regulating the expression of viral or host genes at the posttranscriptional level. The significance of our study is that we revealed the transcriptional regulation mechanism of the antiviral molecule miR-10a after PRRSV infection. Moreover, our research also explained the mechanism of host molecule SRP14, the target gene of miR-10a regulating PRRSV replication. Thus, we report a novel regulatory pathway of IRF8-miR-10a-SRP14 against PRRSV infection, which provides new insights into virus-host interactions and suggests potential new control measures for future PRRSV outbreaks.
微小 RNA（miRNA）在病毒-宿主相互作用中发挥着重要作用。我们之前的工作表明，在猪繁殖与呼吸综合征病毒（PRRSV）感染期间，猪肺泡巨噬细胞（PAMs）中 miR-10a 的表达水平增加，并通过下调宿主分子信号识别颗粒 14（SRP14）蛋白进一步抑制病毒复制。然而，PRRSV 感染后 miR-10a 增加的分子机制尚不清楚。在本研究中，转录因子干扰素调节因子 8（IRF8）被鉴定为 miR-10a 的负调控因子。PRRSV 感染降低了 PAMs 中 IRF8 的表达水平，导致 miR-10a 表达上调，从而发挥抗 PRRSV 作用。同时，本工作首次证明，IRF8 以 miR-10a 依赖的方式促进 PRRSV 复制。此外，我们解释说，miR-10a 的靶基因 SRP14 通过与病毒成分 Nsp2 相互作用促进 PRRSV 基因组的合成，从而促进 PRRSV 复制。总之，我们确定了一个新的针对 PRRSV 感染的 IRF8-miR-10a-SRP14 调控途径，为病毒-宿主相互作用提供了新的见解，并为控制 PRRSV 提供了新的潜在抗病毒策略。
自 20 世纪 80 年代首次发现以来，猪繁殖与呼吸综合征病毒（PRRSV）已迅速传播到全球养猪业，造成了无法估量的经济损失。然而，传统疫苗并不能提供令人满意的保护。了解宿主抵抗 PRRSV 感染的分子机制对于开发安全有效的 PRRSV 控制策略是必要的。在病毒感染过程中，miRNA 在转录后水平上对病毒或宿主基因的表达起着至关重要的调控作用。我们研究的意义在于揭示了 PRRSV 感染后抗病毒分子 miR-10a 的转录调控机制。此外，我们的研究还解释了宿主分子 SRP14（miR-10a 的靶基因）调节 PRRSV 复制的机制。因此，我们报告了一个新的针对 PRRSV 感染的 IRF8-miR-10a-SRP14 调控途径，为病毒-宿主相互作用提供了新的见解，并为未来 PRRSV 爆发提供了新的潜在控制措施。
