Tick-borne encephalitis virus inhibits rRNA synthesis and host protein production in human cells of neural origin

Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus (Flaviviridae), is a causative agent of a severe neuroinfection. Recently, several flaviviruses have been shown to interact with host protein synthesis. In order to determine whether TBEV interacts with this host process in its natural target cells, we analysed de novo protein synthesis in a human cell line derived from cerebellar medulloblastoma (DAOY HTB-186). We observed a significant decrease in the rate of host protein synthesis, including the housekeeping genes HPRT1 and GAPDH and the known interferon-stimulated gene viperin. In addition, TBEV infection resulted in a specific decrease of RNA polymerase I (POLR1) transcripts, 18S and 28S rRNAs and their precursor, 45-47S pre-rRNA, but had no effect on the POLR3 transcribed 5S rRNA levels. To our knowledge, this is the first report of flavivirus-induced decrease of specifically POLR1 rRNA transcripts accompanied by host translational shut-off.蜱传脑炎病毒（Tick-borne encephalitis virus, TBEV）隶属于黄病毒科（Flaviviridae）黄病毒属（Flavivirus），是引发重症神经感染的致病原。近期多项研究证实，多种黄病毒可与宿主蛋白质合成过程发生相互作用。为明确TBEV是否在其天然靶细胞中与该宿主过程发生相互作用，我们对源自小脑髓母细胞瘤的人类细胞系（DAOY HTB-186）的宿主蛋白质从头合成水平进行了检测。结果显示，宿主蛋白质合成速率显著降低，涉及管家基因HPRT1、GAPDH以及已知的干扰素刺激基因病毒抑制蛋白（viperin）。此外，TBEV感染可特异性降低RNA聚合酶I（RNA polymerase I, POLR1）转录的18S、28S核糖体RNA（rRNA）及其前体45-47S核糖体RNA前体的水平，但对RNA聚合酶III（POLR3）转录的5S rRNA水平无影响。据我们所知，本研究首次报道了黄病毒诱导的POLR1特异性核糖体RNA转录本降低，同时伴随宿主翻译关闭。