狂犬病病毒感染N2a细胞引起的转录体差异表达

Differential expression profile in Neuro-2a cells infected by rabies virus

狂犬病是一种人畜共患疾病,对全球公共卫生构成极大威胁。狂犬病病毒(RABV)呈嗜神经性传播,会引发宿主严重的神经功能紊乱,致死率几乎100%。为鉴定RABV影响神经细胞功能的重要基因,本研究采用RNA测序(RNA-seq)方法建立并分析了固定毒株CVS-11感染小鼠神经母细胞瘤细胞(Neuro-2a,N2a)的mRNA表达谱,并通过基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析确定差异表达基因(DEGs)。结果显示,在CVS-11毒株感染的N2a中,共有415个差异表达基因,其中89个为上调基因,326个为下调基因。差异表达基因涉及多种生物学过程,包括轴突传导信号通路、胆固醇代谢通路、氮代谢信号通路、鞘糖脂生物合成信号通路等,其中多种DEGs已被证明与RABV感染密切相关,从中挑选出12个与轴突传导、抗原处理与呈递等通路相关的差异表达基因进行实时荧光定量PCR验证,其变化趋势与RNA-seq结果一致。本研究检测了神经细胞在RABV感染条件下基因转录组变化,为探究RABV感染对神经细胞功能的影响机制提供了新的线索。

Rabies is a zoonotic disease that poses a global public health threat.Rabies virus(RABV) is neurotropic and can cause severe neurological disorders and behavioral abnormalities in host,with a fatality rate nearly 100%.In order to identify the key genes for RABV affecting neuronal cell function,we established and analyzed the mRNA expression profile of Neuro-2a(N2a) cell infected with challenge virus standard(CVS)-11 by RNA sequencing(RNA-seq).Biological functions of differentially expressed genes(DEGs) were determined by GO and KEGG enrichment analysis.The results showed that there were 415 differentially expressed genes in N2a infected with CVS-11 strain,of which 89 were up-regulated and 326 were down-regulated.These genes were related to a variety of biological processes,such as axon guidance pathway,cholesterol metabolism pathway,nitrogen metabolism pathway,and glycosphingolipid biosynthesis pathway,many of them have been shown to be closely associated with RABV infection.A total of 12 DEGs related to axon conduction,antigen processing and presentation pathways were selected and detected by real-time PCR,and their expression trends were consistent with the RNA-seq results.The genomic transcriptomic data on N2a cell under RABV infection will provide new clues for probing the mechanisms of RABV infection and transmission in the nervous system in the future.