Abstract
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.
Highlights
The Flaviviridae family contains arthropod-borne viruses including medically important pathogens with worldwide distribution and impact, such as dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), Japanese encephalitis virus (JEV), Zika virus (ZIKV), and tick-borne encephalitis virus (TBEV) [1].Tick-borne encephalitis virus (TBEV) causes a severe neuroinfection known as tick-borne encephalitis, which affects thousands of people across Eurasia annually [2, 3]
Little is known about the interaction of this neurotropic virus with neural cells, even though this may be important to better understand why or how TBEV can cause high pathogenicity in humans, especially following neural cell infection
The transcriptional shut-off was documented for rRNA species transcribed by RNA polymerase I (18S rRNA, 28S rRNA and their precursor 45-47S prerRNA), but not for RNA polymerase III rRNA transcripts (5S rRNA)
Summary
TBEV causes a severe neuroinfection known as tick-borne encephalitis, which affects thousands of people across Eurasia annually [2, 3]. Understanding the interaction between TBEV and human neural cells is essential as it could lead to possible new treatment targets and a better understanding of why TBEV infection can result in severe neurological symptoms. While the structural proteins are the main building units of the viral particle, the non-structural proteins are crucial in the TBEV life cycle. They are essential components of viral replication within the host endoplasmic reticulum or Golgi apparatus-derived membrane compartments and the virion assembly processes and are involved in immune response evasion/counteractions [14,15,16]
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