Research Paper Volume 12, Issue 17 pp 17503—17527
Transcriptome analysis of duck embryo fibroblasts for the dynamic response to duck tembusu virus infection and dual regulation of apoptosis genes
- 1 Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- 2 Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China
- 3 Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, Sichuan, China
Received: April 14, 2020 Accepted: July 2, 2020 Published: September 7, 2020
https://doi.org/10.18632/aging.103759How to Cite
Abstract
Duck Tembusu virus (DTMUV) is an emerging pathogenic flavivirus that has caused enormous economic losses in Southeast Asia. However, the pathogenic mechanism and host’s responses after DTMUV infection remain poorly understood. During this study, total mRNA sequencing (RNA-Seq) analysis was used to detect the global gene expression in DEFs at various time points after DTMUV infection. We identified 326 genes altered significantly at all time points, and these genes were dynamically enriched in multifarious biological processes, including apoptosis, innate immune response, DNA replication, cell cycle arrest and DNA repair. Next, the results showed that apoptosis was induced and the proportion of apoptosis increased with time, and pro-apoptotic molecules caspases were activated. The RNA-seq data analysis further revealed that most pro-apoptosis and anti-apoptosis genes were early continually responsive, and the genes involved in both intrinsic and extrinsic apoptotic pathways were initiated. Further, the considerably enriched immune-relevant pathways were involved in apoptosis process, and protein-protein interactions (PPIs) analysis showed that IL6, STAT1, TNFAIP3, CFLAR and PTGS2 may be key regulators of DEFs apoptosis. In conclusion, this study not only contributes to understanding the underlying mechanism of DEFs infection with DTMUV, but also provides new insights into targets screening for antiviral therapy.
Abbreviations
DTMUV: Duck Tembusu virus; RNA-Seq: mRNA sequencing; DEFs: duck embryo fibroblasts; PPIs: protein-protein interactions; CPEs: cytopathic effects; ORF: open reading frame; NS: non-structural; DENV: dengue virus; WNV: West Nile virus; ZIKV: Zika virus; HEV: hepatitis E virus; HCV: hepatitis C virus; ZEBOV: Zaire ebola virus; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; DEGs: differentially expressed genes; NBS: newborn bovine serum; DMEM: Dulbecco’s Modified Eagle’s Medium; MOI: multiplicity of infection; PCA: principal component analysis; FPKM: fragments per kilobase of transcript per million mapped reads; FCM: flow cytometry; Q-RT-PCR: Quantitative real-time PCR; SEM: standard error of the mean; ANOVA: analysis of variance; TCID50: tissue culture infective dose; RSAD2: radical S-adenosyl methionine domain-containing protein 2; POMC: proopiomelanocortin; IL12B: interleukin 12B; HMX3: H6 family homeobox 3; HPD: 4-hydroxyphenylpyruvate dioxygenase; SIGLEC15: sialic acid binding Ig like lectin 15; LMOD3: leiomodin 3; MLXIPL: MLX interacting protein like; C7H21orf58: chromosome 7 C21orf58 homolog; IFN: interferon; MAVS: mitochondrial activated antiviral signaling; TRIM: tripartite motif; IRF3: IFN regulatory factor 3; STAT1: signal transducer and activator of transcription 1.