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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F19%3A43899484" target="_blank" >RIV/60076658:12310/19:43899484 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60077344:_____/19:00520507

Výsledek na webu

<a href="https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0007745&type=printable" target="_blank" >https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0007745&type=printable</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pntd.0007745" target="_blank" >10.1371/journal.pntd.0007745</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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. Author summary Tick-borne encephalitis virus (TBEV) is a causative agent of a severe human neuroinfection that threatens Europe and Asia. 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. Here, we showed that TBEV induced host translational shut-off in cells of neural origin. In addition, TBEV interfered also with the expression of host ribosomal RNAs. Interestingly, the transcriptional shut-off was documented for rRNA species transcribed by RNA polymerase I (18S rRNA, 28S rRNA and their precursor 45-47S pre-rRNA), but not for RNA polymerase III rRNA transcripts (5S rRNA). Artificial inhibition of host translation using cycloheximide resulted in the decrease of all rRNA species. Based on these data, TBEV seems to specifically target transcription of RNA polymerase I. These new findings further increase our understanding of TBEV interactions with a key target cell type.

Název v anglickém jazyce

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

Popis výsledku anglicky

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. Author summary Tick-borne encephalitis virus (TBEV) is a causative agent of a severe human neuroinfection that threatens Europe and Asia. 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. Here, we showed that TBEV induced host translational shut-off in cells of neural origin. In addition, TBEV interfered also with the expression of host ribosomal RNAs. Interestingly, the transcriptional shut-off was documented for rRNA species transcribed by RNA polymerase I (18S rRNA, 28S rRNA and their precursor 45-47S pre-rRNA), but not for RNA polymerase III rRNA transcripts (5S rRNA). Artificial inhibition of host translation using cycloheximide resulted in the decrease of all rRNA species. Based on these data, TBEV seems to specifically target transcription of RNA polymerase I. These new findings further increase our understanding of TBEV interactions with a key target cell type.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10607 - Virology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

PLoS Neglected Tropical Diseases

ISSN

1935-2735

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

24

Strana od-do

—

Kód UT WoS článku

000490987100038

EID výsledku v databázi Scopus

2-s2.0-85073126477