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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F22%3A00557410" target="_blank" >RIV/60077344:_____/22:00557410 - isvavai.cz</a>

Alternative codes found

RIV/68081707:_____/22:00557410 RIV/61388963:_____/22:00557410 RIV/00027162:_____/22:N0000035 RIV/00216224:14310/22:00125682 RIV/60460709:41340/22:94084

Result on the web

<a href="https://academic.oup.com/nar/article/50/8/4574/6568495?login=true" target="_blank" >https://academic.oup.com/nar/article/50/8/4574/6568495?login=true</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkac225" target="_blank" >10.1093/nar/gkac225</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

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

Name of the periodical

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

1362-4962

Volume of the periodical

50

Issue of the periodical within the volume

8

Country of publishing house

GB - UNITED KINGDOM

Number of pages

27

Pages from-to

4574-4600

UT code for WoS article

000785763900001

EID of the result in the Scopus database

2-s2.0-85130346646