Tick-borne encephalitis virus inhibits production of ribosomal RNA in human cells of neuronal origin

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F19%3A00521058" target="_blank" >RIV/60077344:_____/19:00521058 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Tick-borne encephalitis virus inhibits production of ribosomal RNA in human cells of neuronal origin

Original language description

Ribosomal RNA (rRNA) contributes to the structure of ribosomes and thus is essential for the protein synthesis process. Transcription of human rRNA is carried out by RNA polymerases I and III (POLR1, POLR3). In more detail, POLR1 yields a single transcription unit 45S pre¬rRNA, which undergoes a complex maturation process resulting in the generation of 5.8S, 18S, and 28S rRNA molecules. POLR3 is responsible for the transcription of 5S rRNA. Tick¬borne encephalitis virus (TBEV) is a member of the genus Flavivirus and can cause serious infections in humans which may result in encephalitis/meningoencephalitis.Our transcriptomic data from TBEV¬infected neural cell line DAOY suggested a possible link between the infection and rRNA production. We therefore analysed the levels of mature 5S, 18S and 28S rRNAs in DAOY cells infected by TBEV. Surprisingly, only levels of POLR1 transcripts, 18S and 28S rRNAs, were significantly reduced upon TBEV infection. Following metabolic labelling experiments using Click chemistry revealed that TBEV decreases the production of nascent RNA, particularly the 45S prerRNA precursor. In order to determine whether the rRNA decrease is a result of virus¬induced translational shut¬off, which was described earlier, we treated cells with cycloheximide (CHX), a translation elongation inhibitor. Subsequent analyses of rRNA levels showed that unlike TBEV, CHX decreased the production of both, POLR1 and POLR3 rRNA transcripts. These data therefore suggests that TBEV may specifically target POLR1 transcription process.This is the first report of flavivirus¬dependent decrease of host rRNA levels, which may contribute to the viral pathogenesis. Further experiments are in progress in order to describe the exact mechanism of observed rRNA decay

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10607 - Virology

Project

<a href="/en/project/GA18-27204S" target="_blank" >GA18-27204S: Interactions of flaviviral genomic and subgenomic RNA with host and viral proteins</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů