Wu Changcheng, Zhang Zhongxian, Li Zhaoqing, Li Ruorui, Huo Shuting, Li Han, Lu Roujian, Tian Houwen, Wang Wenling, Zhao Li, Huang Baoying, Deng Yao, Tan Wenjie
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
School of Public Health, Baotou Medical College, Baotou 014040, China.
Biosaf Health. 2024 Aug 22;6(5):286-297. doi: 10.1016/j.bsheal.2024.08.001. eCollection 2024 Oct.
The vaccinia virus Tiantan (VTT) is widely utilized as a smallpox vaccine in China and holds significant importance in the prevention of diseases stemming from poxvirus infections. Nevertheless, few studies have investigated the influence of VTT infection on host gene expression. In this study, we constructed time series transcriptomic profiles of HeLa cells infected with both VTT and western reserve (WR) strains. We observed similar patterns of viral gene expression, while the expression levels of host genes varied between the two strains. There was an immediate and significant repression of host gene expression, particularly in genes associated with oxidative phosphorylation. Conversely, genes involved in nerve growth factor (NGF)-stimulated transcription were significantly activated. The upregulation of genes linked to the ribonucleic acid (RNA)-induced silencing complex (RISC) suggested a potential role for posttranscriptional regulation in the interaction between the vaccinia virus and the host. In the later stages of infection, pathways such as extracellular matrix organization, neutrophil degranulation, complement and interferon responses, translation, and programmed cell death are largely inhibited. A significant number of host genes exhibit correlations with changes in the expression levels of viral genes. The host genes that are negatively correlated with viral genes are mainly enriched in pathways associated with translation and the response to viral infection. This study significantly contributes to advancing our understanding of the dynamics between the vaccinia virus and the host, improving the application of VTTs and facilitating the development of effective vaccines against diseases such as smallpox and monkeypox.
天坛痘苗病毒（VTT）在中国被广泛用作天花疫苗，在预防痘病毒感染引发的疾病方面具有重要意义。然而，很少有研究调查VTT感染对宿主基因表达的影响。在本研究中，我们构建了感染VTT和西方储备株（WR）的HeLa细胞的时间序列转录组图谱。我们观察到病毒基因表达模式相似，而两株病毒感染的宿主基因表达水平有所不同。宿主基因表达立即受到显著抑制，尤其是与氧化磷酸化相关的基因。相反，参与神经生长因子（NGF）刺激转录的基因被显著激活。与核糖核酸（RNA）诱导沉默复合体（RISC）相关的基因上调表明转录后调控在痘苗病毒与宿主相互作用中可能发挥作用。在感染后期，细胞外基质组织、中性粒细胞脱颗粒、补体和干扰素反应、翻译以及程序性细胞死亡等通路大多受到抑制。大量宿主基因与病毒基因表达水平的变化存在相关性。与病毒基因呈负相关的宿主基因主要富集在与翻译和病毒感染反应相关的通路中。本研究对于增进我们对痘苗病毒与宿主之间动态关系的理解、改善VTT的应用以及推动针对天花和猴痘等疾病的有效疫苗的开发具有重要意义。
