College of veterinary medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.
Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
BMC Genomics. 2019 Oct 24;20(1):774. doi: 10.1186/s12864-019-6120-4.
Bovine viral diarrhoea virus (BVDV) is the member of the genus Pestivirus within the Flaviviridae family and responsible for severe economic losses in the cattle industry. BVDV can employ 'infect-and-persist' strategy and 'hit-and-run' strategy to remain associated with hosts and thus contributes to BVDV circulation in cattle herds. BVDV have also evolved various strategies to evade the innate immunity of host. To further understand the mechanisms by which BVDV overcomes the host cell innate immune response and provide more clues for further understanding the BVDV-host interaction, in this descriptive study, we conducted a investigation of differentially expressed genes (DEGs) of the host during BVDV infection by RNA-Seq analysis.
Our analysis identified 1297, 1732, 3072, and 1877 DEGs in the comparison groups mock vs. MDBK cells infected with BVDV post 2 h (MBV2h), mock vs. MBV6h, mock vs. MBV12h, and mock vs. MBV24h, respectively. The reproducibility and repeatability of the results were validated by RT-qPCR. Enrichment analyses of GO annotations and KEGG pathways revealed the host DEGs that are potentially induced by BVDV infection and may participate in BVDV-host interactions. Protein-protein interaction (PPI) network analyses identified the potential interactions among the DEGs. Our findings suggested that BVDV infection induced the upregulation of genes involved in lipid metabolism. The expression of genes that have antiviral roles, including ISG15, Mx1, OSA1Y, were found to be downregulated and are thus potentially associated with the inhibition of host innate immune system during BVDV infection. The expression levels of F3, C1R, KNG1, CLU, C3, FB, SERPINA5, SERPINE1, C1S, F2RL2, and C2, which belong to the complement and coagulation signalling cascades, were downregulated during BVDV infection, which suggested that the complement system might play a crucial role during BVDV infection.
In this descriptive study, our findings revealed the changes in the host transcriptome expression profile during BVDV infection and suggested that BVDV-infection induced altering the host's metabolic network, the inhibition of the expression of antiviral proteins and genes within the complement system might be contributed to BVDV proliferation. The above findings provided unique insights for further studies on the mechanisms underlying BVDV-host interactions.
牛病毒性腹泻病毒（BVDV）是黄病毒科瘟病毒属的成员，可导致牛养殖业遭受严重的经济损失。BVDV 可采用“感染-持续感染”和“侵袭-逃离”策略与宿主共存，从而促进牛群中 BVDV 的循环。BVDV 还进化出多种策略来逃避宿主的固有免疫。为了进一步了解 BVDV 克服宿主细胞固有免疫应答的机制，并为进一步了解 BVDV-宿主相互作用提供更多线索，在本描述性研究中，我们通过 RNA-Seq 分析研究了 BVDV 感染宿主时宿主差异表达基因（DEGs）。
在比较组中，我们发现模拟组（mock）与感染 BVDV 后 2 小时（MBV2h）、6 小时（MBV6h）、12 小时（MBV12h）和 24 小时（MBV24h）的 MDBK 细胞相比，分别有 1297、1732、3072 和 1877 个 DEGs。通过 RT-qPCR 验证了结果的可重复性和再现性。GO 注释和 KEGG 通路的富集分析揭示了宿主 DEGs，这些基因可能是由 BVDV 感染诱导的，并可能参与 BVDV-宿主相互作用。蛋白质-蛋白质相互作用（PPI）网络分析确定了 DEGs 之间的潜在相互作用。我们的研究结果表明，BVDV 感染诱导了参与脂质代谢的基因上调。抗病毒作用基因的表达，包括 ISG15、Mx1、OSA1Y 的表达下调，表明这些基因可能与 BVDV 感染期间宿主固有免疫系统的抑制有关。F3、C1R、KNG1、CLU、C3、FB、SERPINA5、SERPINE1、C1S、F2RL2 和 C2 的表达水平在 BVDV 感染期间下调，这些基因属于补体和凝血信号级联，这表明补体系统可能在 BVDV 感染过程中发挥关键作用。
在本描述性研究中，我们的研究结果揭示了 BVDV 感染期间宿主转录组表达谱的变化，并表明 BVDV 感染诱导改变了宿主的代谢网络，抑制抗病毒蛋白和补体系统内基因的表达可能有助于 BVDV 的增殖。上述发现为进一步研究 BVDV-宿主相互作用的机制提供了独特的见解。
