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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 n...
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| Published in: | PLoS neglected tropical diseases 2019-09, Vol.13 (9), p.e0007745-e0007745 |
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| container_title | PLoS neglected tropical diseases |
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| creator | Selinger, Martin Tykalová, Hana Štěrba, Ján Věchtová, Pavlína Vavrušková, Zuzana Lieskovská, Jaroslava Kohl, Alain Schnettler, Esther Grubhoffer, Libor |
| description | 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. |
| doi_str_mv | 10.1371/journal.pntd.0007745 |
| format | article |
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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.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0007745</identifier><identifier>PMID: 31560682</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Arachnids ; Biological response modifiers ; Biology ; Biology and life sciences ; Cell Line, Tumor ; Cells (Biology) ; Cerebellum ; Dengue fever ; DNA-directed RNA polymerase ; Encephalitis ; Encephalitis Viruses, Tick-Borne - physiology ; Encephalitis, Tick-Borne - genetics ; Encephalitis, Tick-Borne - metabolism ; Encephalitis, Tick-Borne - virology ; Flaviviruses ; Funding ; Genes ; Genetic aspects ; Genomes ; Gliomas ; Glyceraldehyde-3-phosphate dehydrogenase ; Health aspects ; Humans ; Infection ; Infections ; Influenza ; Interferon ; Medicine and Health Sciences ; Medulloblastoma ; Mortality ; Nucleic acids ; Parasitology ; Penicillin G ; Protein biosynthesis ; Protein Biosynthesis - genetics ; Protein synthesis ; Proteins ; Research and Analysis Methods ; RNA ; RNA polymerase ; RNA Polymerase I - genetics ; RNA Polymerase I - metabolism ; RNA Precursors ; RNA, Ribosomal - genetics ; RNA, Ribosomal - metabolism ; rRNA 5S ; Supervision ; Target cells ; Tick-borne diseases ; Tick-borne encephalitis ; Transcription, Genetic ; Tropical diseases ; Viral infections ; Virology ; Viruses ; West Nile virus ; Zika virus</subject><ispartof>PLoS neglected tropical diseases, 2019-09, Vol.13 (9), p.e0007745-e0007745</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Selinger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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To our knowledge, this is the first report of flavivirus-induced decrease of specifically POLR1 rRNA transcripts accompanied by host translational shut-off.</description><subject>Animals</subject><subject>Arachnids</subject><subject>Biological response modifiers</subject><subject>Biology</subject><subject>Biology and life sciences</subject><subject>Cell Line, Tumor</subject><subject>Cells (Biology)</subject><subject>Cerebellum</subject><subject>Dengue fever</subject><subject>DNA-directed RNA polymerase</subject><subject>Encephalitis</subject><subject>Encephalitis Viruses, Tick-Borne - physiology</subject><subject>Encephalitis, Tick-Borne - genetics</subject><subject>Encephalitis, Tick-Borne - metabolism</subject><subject>Encephalitis, Tick-Borne - virology</subject><subject>Flaviviruses</subject><subject>Funding</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Gliomas</subject><subject>Glyceraldehyde-3-phosphate dehydrogenase</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Infection</subject><subject>Infections</subject><subject>Influenza</subject><subject>Interferon</subject><subject>Medicine and Health Sciences</subject><subject>Medulloblastoma</subject><subject>Mortality</subject><subject>Nucleic acids</subject><subject>Parasitology</subject><subject>Penicillin G</subject><subject>Protein biosynthesis</subject><subject>Protein Biosynthesis - genetics</subject><subject>Protein synthesis</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>RNA</subject><subject>RNA polymerase</subject><subject>RNA Polymerase I - genetics</subject><subject>RNA Polymerase I - metabolism</subject><subject>RNA Precursors</subject><subject>RNA, Ribosomal - genetics</subject><subject>RNA, Ribosomal - metabolism</subject><subject>rRNA 5S</subject><subject>Supervision</subject><subject>Target cells</subject><subject>Tick-borne diseases</subject><subject>Tick-borne encephalitis</subject><subject>Transcription, Genetic</subject><subject>Tropical diseases</subject><subject>Viral infections</subject><subject>Virology</subject><subject>Viruses</subject><subject>West Nile virus</subject><subject>Zika virus</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkl1rHCEUhofS0ny0_6C0QqH0Zrd-zIx6E1hCPwKhhZJei-Oc2XE7qxt1Avn3dbKTsFuCF4o-76vn9RTFO4KXhHHyZePH4PSw3LnULjHGnJfVi-KUSFYtKGfVy4P1SXEW4wbjSlaCvC5OGKlqXAt6WtzeWPN30fjgAIEzsOv1YJON6M6GMSLretvYFFH4_XOF4r1LPcR8ql2Leh8T2gWfwLppbkeTrHdZg_pxqx0yMAwR-Q45GIMekA92bd2b4lWnhwhv5_m8-PPt683lj8X1r-9Xl6vrhalpmRbAq4Z0nNJWcJBYVG1bUtZB2QoJXOhGcE50YyQFQ2sjOyw7yRqoMZRM1A07Lz7sfXeDj2pOKyrKcPbnhPNMXO2J1uuN2gW71eFeeW3Vw4YPa6VDsmYAVYocmKy4YCUpCQfNTYcr3rTCdAIakr0u5tvGZgutAZdyyUemxyfO9mrt71TNRUUYzgafZ4Pgb0eISW1tnBLUDvyY302lJCWWfEI__oc-X91MrXUuwLrO53vNZKpWNWZY0prKTC2fofJoYWuNd9DZvH8k-HQg6EEPqY9-GKevj8dguQdN8DEG6J7CIFhNHfz4ajV1sJo7OMveHwb5JHpsWfYPCqjuPQ</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Selinger, Martin</creator><creator>Tykalová, Hana</creator><creator>Štěrba, Ján</creator><creator>Věchtová, Pavlína</creator><creator>Vavrušková, Zuzana</creator><creator>Lieskovská, Jaroslava</creator><creator>Kohl, Alain</creator><creator>Schnettler, Esther</creator><creator>Grubhoffer, Libor</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-5420-9702</orcidid><orcidid>https://orcid.org/0000-0002-3933-8901</orcidid></search><sort><creationdate>20190901</creationdate><title>Tick-borne encephalitis virus inhibits rRNA synthesis and host protein production in human cells of neural origin</title><author>Selinger, Martin ; Tykalová, Hana ; Štěrba, Ján ; Věchtová, Pavlína ; Vavrušková, Zuzana ; Lieskovská, Jaroslava ; Kohl, Alain ; Schnettler, Esther ; Grubhoffer, Libor</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-e75b1f722d87e9085dd423fe4d89e78ab8771abc92ec26c9f09f93be60e4386b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Arachnids</topic><topic>Biological response modifiers</topic><topic>Biology</topic><topic>Biology and life sciences</topic><topic>Cell Line, Tumor</topic><topic>Cells (Biology)</topic><topic>Cerebellum</topic><topic>Dengue fever</topic><topic>DNA-directed RNA polymerase</topic><topic>Encephalitis</topic><topic>Encephalitis Viruses, Tick-Borne - 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genetics</topic><topic>RNA, Ribosomal - metabolism</topic><topic>rRNA 5S</topic><topic>Supervision</topic><topic>Target cells</topic><topic>Tick-borne diseases</topic><topic>Tick-borne encephalitis</topic><topic>Transcription, Genetic</topic><topic>Tropical diseases</topic><topic>Viral infections</topic><topic>Virology</topic><topic>Viruses</topic><topic>West Nile virus</topic><topic>Zika virus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Selinger, Martin</creatorcontrib><creatorcontrib>Tykalová, Hana</creatorcontrib><creatorcontrib>Štěrba, Ján</creatorcontrib><creatorcontrib>Věchtová, Pavlína</creatorcontrib><creatorcontrib>Vavrušková, Zuzana</creatorcontrib><creatorcontrib>Lieskovská, Jaroslava</creatorcontrib><creatorcontrib>Kohl, Alain</creatorcontrib><creatorcontrib>Schnettler, Esther</creatorcontrib><creatorcontrib>Grubhoffer, Libor</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31560682</pmid><doi>10.1371/journal.pntd.0007745</doi><orcidid>https://orcid.org/0000-0002-5420-9702</orcidid><orcidid>https://orcid.org/0000-0002-3933-8901</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Arachnids Biological response modifiers Biology Biology and life sciences Cell Line, Tumor Cells (Biology) Cerebellum Dengue fever DNA-directed RNA polymerase Encephalitis Encephalitis Viruses, Tick-Borne - physiology Encephalitis, Tick-Borne - genetics Encephalitis, Tick-Borne - metabolism Encephalitis, Tick-Borne - virology Flaviviruses Funding Genes Genetic aspects Genomes Gliomas Glyceraldehyde-3-phosphate dehydrogenase Health aspects Humans Infection Infections Influenza Interferon Medicine and Health Sciences Medulloblastoma Mortality Nucleic acids Parasitology Penicillin G Protein biosynthesis Protein Biosynthesis - genetics Protein synthesis Proteins Research and Analysis Methods RNA RNA polymerase RNA Polymerase I - genetics RNA Polymerase I - metabolism RNA Precursors RNA, Ribosomal - genetics RNA, Ribosomal - metabolism rRNA 5S Supervision Target cells Tick-borne diseases Tick-borne encephalitis Transcription, Genetic Tropical diseases Viral infections Virology Viruses West Nile virus Zika virus |
| title | Tick-borne encephalitis virus inhibits rRNA synthesis and host protein production in human cells of neural origin |
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