Guanine quadruplexes in the RNA genome of the tick-borne
encephalitis virus: their role as a new antiviral target and in
virus biology

J 2022

Guanine quadruplexes in the RNA genome of the tick-borne encephalitis virus: their role as a new antiviral target and in virus biology

HOLOUBEK, Jiří, Klára BEDNÁŘOVÁ, Jan HAVIERNIK, Ivana HUVAROVÁ, Zuzana DVOŘÁKOVÁ et. al.

Základní údaje

Originální název

Guanine quadruplexes in the RNA genome of the tick-borne encephalitis virus: their role as a new antiviral target and in virus biology

Autoři

HOLOUBEK, Jiří (203 Česká republika, garant, domácí), Klára BEDNÁŘOVÁ (203 Česká republika), Jan HAVIERNIK (203 Česká republika), Ivana HUVAROVÁ, Zuzana DVOŘÁKOVÁ, Jiří ČERNÝ, Martina OUTLÁ (203 Česká republika, domácí), Jiří SALÁT (203 Česká republika), Eva KONKOLOVA, Evzen BOURA, Daniel RŮŽEK (203 Česká republika, domácí), Michaela VORLÍČKOVÁ (203 Česká republika), Luděk EYER (203 Česká republika) a Daniel RENČIUK (203 Česká republika)

Vydání

Nucleic Acids Research, Oxford University Press, 2022, 0305-1048

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10607 Virology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 14.900

Kód RIV

RIV/00216224:14310/22:00125682

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1093/nar/gkac225

UT WoS

000785763900001

Klíčová slova česky

guaninový kvadruplex; kvadruplex; sekundární struktura; RNA; virus klíšťové encefalitidy; TBEV; antivirotika

Klíčová slova anglicky

guanine quadruplex; quadruplex; secondary structure; RNA; tick-borne encephalitis virus; antivirotics; TBEV

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 1. 2023 10:28, Mgr. Marie Šípková, DiS.

Anotace

V originále

We have identified seven putative guanine quadruplexes (G4) in the RNA genome of tick-borne encephalitis virus (TBEV), a flavivirus causing thousands of human infections and numerous deaths every year. The formation of G4s was confirmed by biophysical methods on synthetic oligonucleotides derived from the predicted TBEV sequences. TBEV-5, located at the NS4b/NS5 boundary and conserved among all known flaviviruses, was tested along with its mutated variants for interactions with a panel of known G4 ligands, for the ability to affect RNA synthesis by the flaviviral RNA-dependent RNA polymerase (RdRp) and for effects on TBEV replication fitness in cells. G4-stabilizing TBEV-5 mutations strongly inhibited RdRp RNA synthesis and exhibited substantially reduced replication fitness, different plaque morphology and increased sensitivity to G4-binding ligands in cell-based systems. In contrast, strongly destabilizing TBEV-5 G4 mutations caused rapid reversion to the wild-type genotype. Our results suggest that there is a threshold of stability for G4 sequences in the TBEV genome, with any deviation resulting in either dramatic changes in viral phenotype or a rapid return to this optimal level of G4 stability. The data indicate that G4s are critical elements for efficient TBEV replication and are suitable targets to tackle TBEV infection.

Citovat

HOLOUBEK, Jiří, Klára BEDNÁŘOVÁ, Jan HAVIERNIK, Ivana HUVAROVÁ, Zuzana DVOŘÁKOVÁ, Jiří ČERNÝ, Martina OUTLÁ, Jiří SALÁT, Eva KONKOLOVA, Evzen BOURA, Daniel RŮŽEK, Michaela VORLÍČKOVÁ, Luděk EYER a Daniel RENČIUK. Guanine quadruplexes in the RNA genome of the tick-borne encephalitis virus: their role as a new antiviral target and in virus biology. Nucleic Acids Research. Oxford University Press, 2022, roč. 50, č. 8, s. 4574-4600. ISSN 0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gkac225.

@article{1848065,
   author = {Holoubek, Jiří and Bednářová, Klára and Haviernik, Jan and Huvarová, Ivana and Dvořáková, Zuzana and Černý, Jiří and Outlá, Martina and Salát, Jiří and Konkolova, Eva and Boura, Evzen and Růžek, Daniel and Vorlíčková, Michaela and Eyer, Luděk and Renčiuk, Daniel},
   article_number = {8},
   doi = {http://dx.doi.org/10.1093/nar/gkac225},
   keywords = {guanine quadruplex; quadruplex; secondary structure; RNA; tick-borne encephalitis virus; antivirotics; TBEV},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic Acids Research},
   title = {Guanine quadruplexes in the RNA genome of the tick-borne encephalitis virus: their role as a new antiviral target and in virus biology},
   url = {https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkac225/6568495?searchresult=1},
   volume = {50},
   year = {2022}
}

TY  - JOUR
ID  - 1848065
AU  - Holoubek, Jiří - Bednářová, Klára - Haviernik, Jan - Huvarová, Ivana - Dvořáková, Zuzana - Černý, Jiří - Outlá, Martina - Salát, Jiří - Konkolova, Eva - Boura, Evzen - Růžek, Daniel - Vorlíčková, Michaela - Eyer, Luděk - Renčiuk, Daniel
PY  - 2022
TI  - Guanine quadruplexes in the RNA genome of the tick-borne encephalitis virus: their role as a new antiviral target and in virus biology
JF  - Nucleic Acids Research
VL  - 50
IS  - 8
SP  - 4574-4600
EP  - 4574-4600
PB  - Oxford University Press
SN  - 03051048
KW  - guanine quadruplex
KW  - quadruplex
KW  - secondary structure
KW  - RNA
KW  - tick-borne encephalitis virus
KW  - antivirotics
KW  - TBEV
UR  - https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkac225/6568495?searchresult=1
N2  - We have identified seven putative guanine quadruplexes (G4) in the RNA genome of tick-borne encephalitis virus (TBEV), a flavivirus causing thousands of human infections and numerous deaths every year. The formation of G4s was confirmed by biophysical methods on synthetic oligonucleotides derived from the predicted TBEV sequences. TBEV-5, located at the NS4b/NS5 boundary and conserved among all known flaviviruses, was tested along with its mutated variants for interactions with a panel of known G4 ligands, for the ability to affect RNA synthesis by the flaviviral RNA-dependent RNA polymerase (RdRp) and for effects on TBEV replication fitness in cells. G4-stabilizing TBEV-5 mutations strongly inhibited RdRp RNA synthesis and exhibited substantially reduced replication fitness, different plaque morphology and increased sensitivity to G4-binding ligands in cell-based systems. In contrast, strongly destabilizing TBEV-5 G4 mutations caused rapid reversion to the wild-type genotype. Our results suggest that there is a threshold of stability for G4 sequences in the TBEV genome, with any deviation resulting in either dramatic changes in viral phenotype or a rapid return to this optimal level of G4 stability. The data indicate that G4s are critical elements for efficient TBEV replication and are suitable targets to tackle TBEV infection.
ER  -

HOLOUBEK, Jiří, Klára BEDNÁŘOVÁ, Jan HAVIERNIK, Ivana HUVAROVÁ, Zuzana DVOŘÁKOVÁ, Jiří ČERNÝ, Martina OUTLÁ, Jiří SALÁT, Eva KONKOLOVA, Evzen BOURA, Daniel RŮŽEK, Michaela VORLÍČKOVÁ, Luděk EYER a Daniel RENČIUK. Guanine quadruplexes in the RNA genome of the tick-borne encephalitis virus: their role as a new antiviral target and in virus biology. \textit{Nucleic Acids Research}. Oxford University Press, 2022, roč.~50, č.~8, s.~4574-4600. ISSN~0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gkac225.

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