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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\u0394HEL1) known to stimulate RNAi and we analyzed how Dicer\u0394HEL1\/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\u0394HEL1\/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\u0394HEL1 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.<\/jats:p>","DOI":"10.1093\/nar\/gkae1288","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T08:29:13Z","timestamp":1736411353000},"source":"Crossref","is-referenced-by-count":7,"title":["Enhanced RNAi does not provide efficient innate antiviral immunity in mice"],"prefix":"10.1093","volume":"53","author":[{"given":"Marcos Iuri\u00a0Roos","family":"Kulmann","sequence":"first","affiliation":[{"name":"Laboratory of Epigenetic Regulations, Institute of Molecular Genetics of the Czech Academy of Sciences , Videnska 1083, 142 20, Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliska","family":"Taborska","sequence":"additional","affiliation":[{"name":"Laboratory of Epigenetic Regulations, Institute of Molecular Genetics of the Czech Academy of Sciences , Videnska 1083, 142 20, Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigita","family":"Benk\u00f6ova","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Enterovirus Laboratory, Institute of Microbiology, Slovak Medical University , Limbova 12, 83303 Bratislava ,","place":["Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Palus","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Biology Centre of the Czech Academy of Sciences , Branisovska 31, CZ-37005 Ceske Budejovice,","place":["Czech Republic"]},{"name":"Laboratory of Emerging Viral Infections, Veterinary Research Institute , Hudcova 70, CZ-62100 Brno,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ales","family":"Drobek","sequence":"additional","affiliation":[{"name":"Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech 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Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Pellerova","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Enterovirus Laboratory, Institute of Microbiology, Slovak Medical University , Limbova 12, 83303 Bratislava ,","place":["Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Borsanyiova","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Enterovirus Laboratory, Institute of Microbiology, Slovak Medical University , Limbova 12, 83303 Bratislava ,","place":["Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Nedvedova","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Biology Centre of the Czech Academy of Sciences , Branisovska 31, CZ-37005 Ceske Budejovice,","place":["Czech Republic"]},{"name":"Faculty of Science, University of South Bohemia , Branisovska 1645\/31a, CZ-37005 Ceske Budejovice ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2735-3311","authenticated-orcid":false,"given":"Ondrej","family":"Stepanek","sequence":"additional","affiliation":[{"name":"Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences , Videnska 1083 , 142 20, Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8423-5565","authenticated-orcid":false,"given":"Shubhada","family":"Bopegamage","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Enterovirus Laboratory, Institute of Microbiology, Slovak Medical University , Limbova 12, 83303 Bratislava 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