Ma Yingying, Wang Li, Jiang Xiaoxia, Yao Xin, Huang Xinning, Zhou Kun, Yang Yaqi, Wang Yixin, Sun Xiaobo, Guan Xueting, Xu Yigang
College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
College of Animal Science and Technology, Northeast Agricultural University, Harbin, China.
Front Immunol. 2022 Mar 16;13:862828. doi: 10.3389/fimmu.2022.862828. eCollection 2022.
Bovine viral diarrhea virus (BVDV) is the causative agent of bovine viral diarrhea-mucosal disease (BVD-MD), an important viral disease in cattle that is responsible for extensive economic losses to the cattle industry worldwide. Currently, several underlying mechanisms involved in viral replication, pathogenesis, and evading host innate immunity of BVDV remain to be elucidated, particularly during the early stage of virus infection. To further explore the mechanisms of BVDV-host interactions, the transcriptomics and proteomics profiles of BVDV-infected MDBK cells were sequenced using RNA-seq and iTRAQ techniques, respectively, and followed by an integrative analysis. Compared with mock-infected MDBK cells, a total of 665 differentially expressed genes (DEGs) (391 down-regulated, 274 up-regulated) and 725 differentially expressed proteins (DEPs) (461 down-regulated, 264 up-regulated) were identified. Among these, several DEGs and DEPs were further verified using quantitative RT-PCR and western blot. Following gene ontology (GO) annotation and KEGG enrichment analysis, we determined that these DEGs and DEPs were significantly enriched in multiple important cellular signaling pathways including NOD-like receptor, Toll-like receptor, TNF, NF-κB, MAPK, cAMP, lysosome, protein processing in endoplasmic reticulum, lipid metabolism, and apoptosis signaling pathways. Significantly, the down-regulated DEGs and DEPs were predominantly associated with apoptosis-regulated elements, inflammatory factors, and antiviral elements that were involved in innate immunity, thus, indicating that BVDV could inhibit apoptosis and the expression of host antiviral genes to facilitate viral replication. Meanwhile, up-regulated DEGs and DEPs were primarily involved in metabolism and autophagy signaling pathways, indicating that BVDV could utilize the host metabolic resources and cell autophagy to promote replication. However, the potential mechanisms BVDV-host interactions required further experimental validation. Our data provide an overview of changes in transcriptomics and proteomics profiles of BVDV-infected MDBK cells, thus, providing an important basis for further exploring the mechanisms of BVDV-host interactions.
牛病毒性腹泻病毒（BVDV）是牛病毒性腹泻-黏膜病（BVD-MD）的病原体，这是一种牛的重要病毒性疾病，给全球养牛业造成了巨大经济损失。目前，BVDV在病毒复制、发病机制以及逃避宿主天然免疫方面的几种潜在机制仍有待阐明，尤其是在病毒感染的早期阶段。为了进一步探究BVDV与宿主相互作用的机制，分别使用RNA测序（RNA-seq）和同位素标记相对和绝对定量（iTRAQ）技术对感染BVDV的MDBK细胞的转录组学和蛋白质组学图谱进行测序，随后进行综合分析。与 mock 感染的 MDBK 细胞相比，共鉴定出 665 个差异表达基因（DEG）（391 个下调，274 个上调）和 725 个差异表达蛋白（DEP）（461 个下调，264 个上调）。其中，若干DEG和DEP通过定量逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法进一步验证。经过基因本体（GO）注释和京都基因与基因组百科全书（KEGG）富集分析，我们确定这些DEG和DEP在多个重要细胞信号通路中显著富集，包括NOD样受体、Toll样受体、肿瘤坏死因子（TNF）、核因子κB（NF-κB）、丝裂原活化蛋白激酶（MAPK）、环磷酸腺苷（cAMP）、溶酶体、内质网中的蛋白质加工、脂质代谢和凋亡信号通路。值得注意的是，下调的DEG和DEP主要与参与天然免疫的凋亡调节元件、炎症因子和抗病毒元件相关，因此表明BVDV可抑制凋亡和宿主抗病毒基因的表达以促进病毒复制。同时，上调的DEG和DEP主要参与代谢和自噬信号通路，表明BVDV可利用宿主代谢资源和细胞自噬来促进复制。然而，BVDV与宿主相互作用的潜在机制需要进一步的实验验证。我们的数据概述了感染BVDV的MDBK细胞转录组学和蛋白质组学图谱的变化，从而为进一步探究BVDV与宿主相互作用的机制提供了重要依据。
