African Swine Fever Virus and Host Response: Transcriptome Profiling of the Georgia 2007/1 Strain and Porcine Macrophages.
African Swine Fever Virus and Host Response: Transcriptome Profiling of the Georgia 2007/1 Strain and Porcine Macrophages.
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DOI：
10.1128/jvi.01939-21
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发表时间：
2022-03-09
影响因子：
5.4
通讯作者：
Werner F
中科院分区：
文献类型：
--
作者：
Cackett G;Portugal R;Matelska D;Dixon L;Werner F
非洲猪瘟病毒（ASFV）对全球经济产生重大影响。由于家猪的病死率接近100%，它目前对畜牧业构成了最大的威胁。虽然已经鉴定了减毒和高毒力ASFV毒株之间的基因组差异，但在基因表达水平上毒力的分子决定因素仍然不透明。在这里，我们的特点ASFV基因型II格鲁吉亚2007/1（GRG）在感染的生理相关的宿主细胞，猪巨噬细胞的转录组。本研究应用CAGE-seq技术对感染后5 h和16 h病毒mRNA的5′端进行了定位。围绕转录起始位点（TSS）的序列背景的生物信息学分析使我们能够表征GRG的全球早期和晚期启动子景观。我们比较了GRG分离株和实验室减毒BA 71 V株的转录组图谱，突出了属于多基因家族的GRG毒力特异性转录物，包括两个预测的MGF 100基因，I7 L和I8 L。同时，我们监测了感染的宿主巨噬细胞中的转录组变化。在研究的9，384个巨噬细胞基因中，652个宿主基因的转录本在感染后5和16 h之间差异调节，而未感染细胞和感染后5 h之间仅25个。NF-κB激活基因和溶酶体成分如S100上调，趋化因子如CCL 24、CXCL 2、CXCL 5和CXCL 8下调。非洲猪瘟病毒（ASFV）引起家猪出血热，病死率接近100%，没有批准的疫苗或抗病毒药物。高毒力的ASFV格鲁吉亚2007/1株（GRG）是2007年ASFV从非洲传播到高加索地区时第一个分离出来的毒株，然后传播到东欧，最近又传播到亚洲。我们使用了一种基于RNA的下一代测序技术CAGE-seq来绘制GRG DNA基因组中病毒基因的起始位置。这使我们能够研究哪些病毒基因在感染的早期或晚期表达，以及如何控制，将它们的表达与无毒力的ASFV-BA 71 V毒株进行比较，以确定在毒力中发挥作用的关键基因。与此同时，我们研究了宿主细胞如何对感染作出反应，这揭示了ASFV如何抑制宿主免疫反应的组分，以最终赢得与猪宿主的军备竞赛。
African swine fever virus (ASFV) has a major global economic impact. With a case fatality in domestic pigs approaching 100%, it currently presents the largest threat to animal farming. Although genomic differences between attenuated and highly virulent ASFV strains have been identified, the molecular determinants for virulence at the level of gene expression have remained opaque. Here, we characterize the transcriptome of ASFV genotype II Georgia 2007/1 (GRG) during infection of the physiologically relevant host cells, porcine macrophages. In this study, we applied cap analysis gene expression sequencing (CAGE-seq) to map th0e 5′ ends of viral mRNAs at 5 and 16 h postinfection. A bioinformatics analysis of the sequence context surrounding the transcription start sites (TSSs) enabled us to characterize the global early and late promoter landscape of GRG. We compared transcriptome maps of the GRG isolate and the lab-attenuated BA71V strain that highlighted GRG virulence-specific transcripts belonging to multigene families, including two predicted MGF 100 genes, I7L and I8L. In parallel, we monitored transcriptome changes in the infected host macrophage cells. Of the 9,384 macrophage genes studied, transcripts for 652 host genes were differentially regulated between 5 and 16 h postinfection compared with only 25 between uninfected cells and 5 h postinfection. NF-κB activated genes and lysosome components such as S100 were upregulated, and chemokines such as CCL24, CXCL2, CXCL5, and CXCL8 were downregulated. IMPORTANCE African swine fever virus (ASFV) causes hemorrhagic fever in domestic pigs, with case fatality rates approaching 100% and no approved vaccines or antivirals. The highly virulent ASFV Georgia 2007/1 strain (GRG) was the first isolated when ASFV spread from Africa to the Caucasus region in 2007, then spreading through Eastern Europe and, more recently, across Asia. We used an RNA-based next-generation sequencing technique called CAGE-seq to map the starts of viral genes across the GRG DNA genome. This has allowed us to investigate which viral genes are expressed during early or late stages of infection and how this is controlled, comparing their expression to the nonvirulent ASFV-BA71V strain to identify key genes that play a role in virulence. In parallel, we investigated how host cells respond to infection, which revealed how the ASFV suppresses components of the host immune response to ultimately win the arms race against its porcine host.
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影响因子：
6.7
作者：
Castelló A;Quintas A;Sánchez EG;Sabina P;Nogal M;Carrasco L;Revilla Y
通讯作者：
Revilla Y
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
3.3
作者：
Gallardo, C.;Nurmoja, I;Arias, M.
通讯作者：
Arias, M.
影响因子：
5.4
作者：
Afonso, CL;Piccone, ME;Rock, DL
通讯作者：
Rock, DL
影响因子：
5.4
作者：
Alejo, Alf;Matamoros, Tania;Andres, German
通讯作者：
Andres, German