Vaccinia virus Tiantan strain blocks host antiviral innate immunity and programmed cell death by disrupting gene expression

IF 3.5 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH
Changcheng Wu , Zhongxian Zhang , Zhaoqing Li , Ruorui Li , Shuting Huo , Han Li , Roujian Lu , Houwen Tian , Wenling Wang , Li Zhao , Baoying Huang , Yao Deng , Wenjie Tan
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Abstract

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.
通过破坏基因表达阻断宿主的抗病毒先天免疫和程序性细胞死亡
疫苗病毒 "天坛"(VTT)在中国被广泛用作天花疫苗,在预防由痘病毒感染引起的疾病方面具有重要意义。然而,很少有研究探讨 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 Western Reserve(WR)毒株的 HeLa 细胞的时间序列转录组图谱。我们观察到病毒基因表达的相似模式,而宿主基因的表达水平在两种毒株之间存在差异。宿主基因的表达立即受到明显抑制,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)刺激转录的基因则被显著激活。与核糖核酸(RNA)诱导沉默复合体(RISC)相关的基因上调表明,转录后调控在疫苗病毒与宿主的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、翻译和细胞程序性死亡等途径在很大程度上受到抑制。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集中在与翻译和病毒感染反应相关的通路中。这项研究极大地促进了我们对疫苗病毒与宿主之间动态关系的理解,提高了 VTTs 的应用水平,并有助于开发有效的疫苗来预防天花和猴痘等疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biosafety and Health
Biosafety and Health Medicine-Infectious Diseases
CiteScore
7.60
自引率
0.00%
发文量
116
审稿时长
66 days
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