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

Tykalová, H., Selinger, M., Štěrba, J., Vavrušková, Z., Věchtová, P., Lieskovská, J., Kohl, A. , Schnettler, E. and Grubhoffer, L. (2019) Tick-borne encephalitis virus inhibits rRNA synthesis and host protein production in human cells of neural origin. PLoS Neglected Tropical Diseases, 13(9), e0007745. (doi: 10.1371/journal.pntd.0007745) (PMID:31560682) (PMCID:PMC6785130)

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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.

Item Type:Articles
Additional Information:MS, HT, JS, PV, ZV and LG were supported by the Ministry of Education, Youth and Sports of the Czech Republic INTER-ACTION projects LTARF 18021, LTAUSA 18040 (http://www.msmt.cz), and the Grant Agency of the Czech Republic (18-27204S; https://gacr.cz). Access to instruments and other facilities was supported by the Czech research infrastructure for systems biology C4SYS (project no LM2015055; http://www.msmt.cz). ES is supported by the DZIF (Deutsches Zentrum für Infektionsforschung; http://www.dzif.de/en/).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Selinger, Mr Martin and Schnettler, Dr Esther and Kohl, Professor Alain
Authors: Tykalová, H., Selinger, M., Štěrba, J., Vavrušková, Z., Věchtová, P., Lieskovská, J., Kohl, A., Schnettler, E., and Grubhoffer, L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Published Online:27 September 2019
Copyright Holders:Copyright © 2019 Selinger et al.
First Published:First published in PLoS Neglected Tropical Diseases 13(9):e0007745
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656551Arbovirus interactions with arthropod hostsAlain KohlMedical Research Council (MRC)MC_UU_12014/8MVLS III - CENTRE FOR VIRUS RESEARCH