Enhanced RNAi does not provide efficient innate antiviral immunity in mice

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F25%3A00642229" target="_blank" >RIV/60077344:_____/25:00642229 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/25:00642229 RIV/60076658:12310/25:43909734 RIV/00216224:14310/25:00140568 RIV/00027162:_____/25:N0000012

Výsledek na webu

<a href="https://academic.oup.com/nar/article/53/1/gkae1288/7945392" target="_blank" >https://academic.oup.com/nar/article/53/1/gkae1288/7945392</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkae1288" target="_blank" >10.1093/nar/gkae1288</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Enhanced RNAi does not provide efficient innate antiviral immunity in mice

Popis výsledku v původním jazyce

In RNA interference (RNAi), long double-stranded RNA is cleaved by the Dicer endonuclease into small interfering RNAs (siRNAs), which guide degradation of complementary RNAs. While RNAi mediates antiviral innate immunity in plants and many invertebrates, vertebrates have adopted a sequence-independent response and their Dicer produces siRNAs inefficiently because it is adapted to process small hairpin microRNA precursors in the gene-regulating microRNA pathway. Mammalian endogenous RNAi is thus a rudimentary pathway of unclear significance. To investigate its antiviral potential, we modified the mouse Dicer locus to express a truncated variant (Dicer ΔHEL1 ) known to stimulate RNAi and we analyzed how Dicer ΔHEL1/wt mice respond to four RNA viruses: coxsackievirus B3 and encephalomyocarditis virus from Picornaviridae, tick-borne encephalitis virus from Flaviviridae, and lymphocytic choriomeningitis virus (LCMV) from Arenaviridae. Increased Dicer activity in Dicer ΔHEL1/wt mice did not elicit any antiviral effect, supporting an insignificant antiviral function of endogenous mammalian RNAi in vivo. However, we also observed that sufficiently high expression of DicerΔHEL1 suppressed LCMV in embryonic stem cells and in a transgenic mouse model. Altogether, mice with increased Dicer activity offer a new benchmark for identifying and studying viruses susceptible to mammalian RNAi in vivo.

Název v anglickém jazyce

Enhanced RNAi does not provide efficient innate antiviral immunity in mice

Popis výsledku anglicky

In RNA interference (RNAi), long double-stranded RNA is cleaved by the Dicer endonuclease into small interfering RNAs (siRNAs), which guide degradation of complementary RNAs. While RNAi mediates antiviral innate immunity in plants and many invertebrates, vertebrates have adopted a sequence-independent response and their Dicer produces siRNAs inefficiently because it is adapted to process small hairpin microRNA precursors in the gene-regulating microRNA pathway. Mammalian endogenous RNAi is thus a rudimentary pathway of unclear significance. To investigate its antiviral potential, we modified the mouse Dicer locus to express a truncated variant (Dicer ΔHEL1 ) known to stimulate RNAi and we analyzed how Dicer ΔHEL1/wt mice respond to four RNA viruses: coxsackievirus B3 and encephalomyocarditis virus from Picornaviridae, tick-borne encephalitis virus from Flaviviridae, and lymphocytic choriomeningitis virus (LCMV) from Arenaviridae. Increased Dicer activity in Dicer ΔHEL1/wt mice did not elicit any antiviral effect, supporting an insignificant antiviral function of endogenous mammalian RNAi in vivo. However, we also observed that sufficiently high expression of DicerΔHEL1 suppressed LCMV in embryonic stem cells and in a transgenic mouse model. Altogether, mice with increased Dicer activity offer a new benchmark for identifying and studying viruses susceptible to mammalian RNAi in vivo.

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

1362-4962

Svazek periodika

53

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

gkae1288

Kód UT WoS článku

001391535800001

EID výsledku v databázi Scopus

2-s2.0-85214572319