Informace o publikaci
Enhanced RNAi does not provide efficient innate antiviral immunity in mice
| Autoři | |
|---|---|
| Rok publikování | 2025 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Nucleic Acids Research |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://doi.org/10.1093/nar/gkae1288 |
| Doi | http://dx.doi.org/10.1093/nar/gkae1288 |
| Klíčová slova | DOUBLE-STRANDED-RNA; HUMAN DICER; VIRUS-REPLICATION; INTERFERENCE; INHIBITION; EXPRESSION; CELLS; BIOGENESIS; ARGONAUTE2; INFECTION |
| Popis | 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?HEL1) known to stimulate RNAi and we analyzed how Dicer?HEL1/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?HEL1/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 Dicer?HEL1 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. |