MicroRNAs(miRNAs)在病毒与宿主的相互作用中起着重要作用。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的表达水平升高,并通过下调宿主分子信号识别颗粒14(SRP14)蛋白的表达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的负调节因子.PRRSV感染降低PAMs中IRF8的表达水平,导致miR-10a表达上调,发挥抗PRRSV作用。同时,这项工作首次证明IRF8以依赖miR-10a的方式促进PRRSV复制.Further,我们解释了miR-10a的靶基因SRP14,通过与病毒组分Nsp2相互作用促进PRRSV基因组的合成,从而促进PRRSV复制。总之,我们发现了一种新的抗PRRSV感染的IRF8-miR-10a-SRP14调控途径,这为病毒与宿主的相互作用提供了新的见解,并提出了控制PRRSV的潜在新抗病毒策略。重要性猪繁殖与呼吸综合征病毒(PRRSV)自1980年代首次发现以来,已迅速传播到全球养猪业,并造成了无法估量的经济损失。然而,常规疫苗不能提供令人满意的保护。了解宿主对PRRSV感染耐药的分子机制对于制定安全有效的PRRSV控制策略是必要的。在病毒感染期间,miRNA在转录后水平上调节病毒或宿主基因的表达中起着至关重要的作用。我们的研究意义在于我们揭示了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调控PRRSV复制的靶基因的机制。因此,我们报道了IRF8-miR-10a-SRP14抗PRRSV感染的新调控途径,这提供了对病毒-宿主相互作用的新见解,并为未来PRRSV爆发提出了潜在的新控制措施。
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. IMPORTANCE 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.