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全基因组转录组分析高度致病毒非洲猪瘟病毒感染揭示了复杂而独特的病毒-宿主相互作用。

Genome-wide transcriptomic analysis of highly virulent African swine fever virus infection reveals complex and unique virus host interaction.

机构信息

School of Medicine, Tsinghua University, Beijing, 100084, China.

State Key Laboratory of Veterinary Biotechnology and National High Containment Laboratory for Animal Diseases Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.

出版信息

Vet Microbiol. 2021 Oct;261:109211. doi: 10.1016/j.vetmic.2021.109211. Epub 2021 Aug 16.

DOI:10.1016/j.vetmic.2021.109211
PMID:34481273
Abstract

African swine fever virus (ASFV), one of the most devastating emerging swine pathogens in China, causes nearly 100 % mortality in naive herds. Here, whole-transcriptome RNA-seq analysis was conducted in porcine alveolar macrophages (PAMs) infected with Pig/Heilongjiang/2018 (Pig/HLJ/18) ASFV at different time points. Our data suggested that ASFV genes expression demonstrated a time-depended pattern and ASFV early genes were involved in antagonizing host innate immunity. Moreover, viral small RNA (vsRNA) was generated as well. Meanwhile, transcriptome analysis of host genes suggested a strong inhibition host immunity-related genes by ASFV infection in PAMs, while enhanced chemokine-mediated signaling pathways and neutrophil chemotaxis were observed in ASFV infected PAMs. Furthermore, ASFV infection also down-regulated host microRNAs (miRNAs) that putatively targeted viral genes, while also triggering dysregulation of host metabolism that promoted virus replication at transcription level. Most importantly, infection of PAMs with ASFV induced a different transcriptome pattern from that of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV), which is known to trigger a host cytokine storm. In conclusion, our transcriptome data implied that ASFV infection in PAMs appeared to be associated with strong inhibition of host immune responses, dysregulation of host chemokine axis and metabolic pathways.

摘要

非洲猪瘟病毒(ASFV)是中国最具破坏性的新兴猪病病原体之一,在无免疫力的猪群中几乎导致 100%的死亡率。在这里,我们对感染了 Pig/Heilongjiang/2018(Pig/HLJ/18)ASFV 的猪肺泡巨噬细胞(PAMs)在不同时间点进行了全转录组 RNA-seq 分析。我们的数据表明,ASFV 基因的表达表现出时间依赖性模式,ASFV 早期基因参与拮抗宿主固有免疫。此外,还产生了病毒小 RNA(vsRNA)。同时,宿主基因的转录组分析表明,ASFV 感染强烈抑制了 PAMs 中的宿主免疫相关基因,而感染的 PAMs 中观察到趋化因子介导的信号通路和中性粒细胞趋化作用增强。此外,ASFV 感染还下调了宿主可能靶向病毒基因的 microRNAs(miRNAs),同时也触发了宿主代谢的失调,从而在转录水平促进了病毒的复制。最重要的是,PAMs 感染 ASFV 引起的转录组模式与已知引发宿主细胞因子风暴的高致病性猪繁殖与呼吸综合征病毒(HP-PRRSV)不同。总之,我们的转录组数据表明,PAMs 中的 ASFV 感染似乎与宿主免疫反应的强烈抑制、宿主趋化因子轴和代谢途径的失调有关。

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