Du Kun, Xia Yu, Wu Qian, Yin Miao, Zhao Hong, Chen Xi-Wen
Animal Disease Prevention and Control and Healthy Breeding Engineering Technology Research Centre, Mianyang Normal University, Mianyang, China.
Front Immunol. 2025 Jan 13;15:1506371. doi: 10.3389/fimmu.2024.1506371. eCollection 2024.
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen that has caused severe economic losses in the swine industry. Screening key host immune-related genetic factors in the porcine alveolar macrophages (PAMs) is critical to improve the anti-virial ability in pigs.
In this study, an model was set to evaluate the anti-PRRSV effect of tylvalosin tartrates. Then, strand-specific RNA-sequencing (ssRNA-seq) and miRNA-sequencing (miRNA-seq) were carried out to profile the whole transcriptome of PAMs in the negative control, PRRSV-infected, and tylvalosin tartrates-treatment group.
The ssRNA-seq identified 11740 long non-coding RNAs in PAMs. Based on our attention mechanism-improved graph convolutional network, 41.07% and 28.59% lncRNAs were predicted to be located in the nucleus and cytoplasm, respectively. The miRNA-seq revealed that tylvalosin tartrates-enhanced miRNAs might play roles in regulating angiogenesis and innate immune-related functions, and it rescued the expression of three anti-inflammation miRNAs (, , and ) that were downregulated due to PRRSV infection. The cytoplasmic lncRNAs enhanced by tylvalosin tartrates might form ceRNA networks with miRNAs to regulate PAM chemotaxis. While cytoplasmic lncRNAs that were rescued by tylvalosin tartrates might protect PAMs via efferocytosis-related ceRNA networks. On the other hand, the tylvalosin tartrates-rescued nuclear lncRNAs might negatively regulate T cell apoptosis and bind to key anti-inflammation factor IL37 to protect the lungs by - and -regulation.
Our data provides a catalog of key non-coding RNAs in response to PRRSV and tylvalosin tartrates and might enrich the genetic basis for future PRRSV prevention and control.
猪繁殖与呼吸综合征病毒(PRRSV)是一种在养猪业中造成严重经济损失的主要病原体。筛选猪肺泡巨噬细胞(PAM)中关键的宿主免疫相关遗传因素对于提高猪的抗病毒能力至关重要。
在本研究中,建立了一个模型来评估酒石酸泰万菌素的抗PRRSV效果。然后,进行链特异性RNA测序(ssRNA-seq)和微小RNA测序(miRNA-seq),以分析阴性对照组、PRRSV感染组和酒石酸泰万菌素处理组中PAM的全转录组。
ssRNA-seq在PAM中鉴定出11740个长链非编码RNA。基于我们改进注意力机制的图卷积网络,分别预测41.07%和28.59%的长链非编码RNA位于细胞核和细胞质中。miRNA-seq显示,酒石酸泰万菌素增强的miRNA可能在调节血管生成和先天免疫相关功能中发挥作用,并且它挽救了三种因PRRSV感染而下调的抗炎miRNA(、和)的表达。酒石酸泰万菌素增强的细胞质长链非编码RNA可能与miRNA形成竞争性内源RNA(ceRNA)网络来调节PAM趋化性。而酒石酸泰万菌素挽救的细胞质长链非编码RNA可能通过与胞葬作用相关的ceRNA网络保护PAM。另一方面,酒石酸泰万菌素挽救的细胞核长链非编码RNA可能通过和调节负向调节T细胞凋亡并与关键抗炎因子IL37结合以保护肺部。
我们的数据提供了应对PRRSV和酒石酸泰万菌素的关键非编码RNA目录,并可能丰富未来PRRSV防控的遗传基础。