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Enhanced RNAi does not provide efficient innate antiviral immunity in mice

MIR. Kulmann, E. Taborska, B. Benköova, M. Palus, A. Drobek, F. Horvat, J. Pasulka, R. Malik, E. Salyova, V. Hönig, M. Pellerova, M. Borsanyiova, L. Nedvedova, O. Stepanek, S. Bopegamage, D. Ruzek, P. Svoboda

. 2025 ; 53 (1) : . [pub] 20250107

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25010316

Grantová podpora
20-03950X Czech Science Foundation
European Research Council - International
647403 European Union's Horizon
Charles University
23-08039S Czech Science Foundation
LX22NPO5103 National Institute of Virology and Bacteriology
European Union-Next Generation EU
68378050 Czech Academy of Sciences
Ministry of Education
LM2023050 MEYS
ID:90254 e-INFRA CZ
90255 ELIXIR-CZ

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 (DicerΔHEL1) known to stimulate RNAi and we analyzed how DicerΔHEL1/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 DicerΔHEL1/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.

Citace poskytuje Crossref.org

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