Screening Core Genes And Signaling Pathways After SFTSV Infection By Integrated Transcriptome Profiling Analysis

Objective: Severe fever with thrombocytopenia syndrome(SFTS)is an emerging tick-borne infectious disease caused by fever with thrombocytopenia syndrome virus(SFTSV),which was first identified in central China in 2009.SFTSV belongs to the family Bunyavirales,Phenuiviridae,genus Bandavirus.Since its first detection,SFTS has spread from eastern China,where it was first identified,to central and western China and even Japan,Korea,and Vietnam.With the SFTSV vectors spread,the morbidity and mortality rates of SFTS are increasing.SFTSV infection can rapidly lead to multi-organ failure and death of the host.In addition,the World Health Organization(WHO)has ranked SFTSV as one of the viruses of greatest concern,but the pathogenesis of the virus remains largely unknown,and there is no effective vaccine or antiviral drug for SFTSV.Method: In this study,based on high-throughput RNA sequencing(RNA-seq),HEK293 cells were treated with SFTSV and MOCK,and the transcriptome was sequenced at 6,12,24 and 48 hours after treatment.The human genome(homo sapiens)was used as the reference genome for comparison,and the FPKM method was used to calculate the gene expression and set the reference parameter(|log2FC|≥1,P≤0.05)to screen the differentially expressed genes.The differentially expressed genes were also subjected to functional enrichment analysis and differential expression analysis to further investigate the interaction between SFTSV and the host.Results: In this study,a total of 9500 genes were identified in response to SFTSV infection,and a total of 1145 differentially expressed genes were screened by bioinformatics analysis,accounting for 12% of the identified host genes.Among them,115,191,259 and 660 differentially expressed genes were identified at 6,12,24 and48 hours,respectively.We found that SFTSV infection induced upregulation of many genes involved in related pathways of cytokine regulation,including TNF,CXCL1,CXCL2,CXCL3,CXCL8,CXCL10 and CCL20,while genes involved in signaling pathways related to platelet activation,such as GNA13,ARHGEF1,ARHGEF12,ROHA,ROCK1 and MYL12 A,which were significantly downregulated after SFTSV infection.This suggests that SFTSV infection causes many inflammatory responses signaling pathways to be upregulated and mediates the production of many cellular inflammatory factors.In addition,it also reveals that SFTSV infection will also cause thrombocytopenia by inhibiting platelet activation.The differentially expressed genes identified in this study will be more useful for further understanding of SFTSV-host interactions and pathogenesis.Conclusion: 1.SFTSV infection causes differential gene expression in host cells that varies across the time course of infection,with the most differentially expressed genes being upregulated at 24 hours;2.GO and KEGG analysis of differentially expressed genes indicate that pre-infection is mostly involved in signal recognition and transduction,while post-infection hosts are more responsive to relevant biological functions such as inflammatory response and cytokine correlation;3.SFTSV infection leads to reduced platelet production by inhibiting platelet activation and other related signaling pathways.