@article{23035daaecac49bbaf3c73b3ba7bd263,
title = "Invading viral DNA triggers dsRNA synthesis by RNA polymerase II to activate antiviral RNA interference in Drosophila",
abstract = "dsRNA sensing triggers antiviral responses against RNA and DNA viruses in diverse eukaryotes. In Drosophila, Invertebrate iridescent virus 6 (IIV-6), a large DNA virus, triggers production of small interfering RNAs (siRNAs) by the dsRNA sensor Dicer-2. Here, we show that host RNA polymerase II (RNAPII) bidirectionally transcribes specific AT-rich regions of the IIV-6 DNA genome to generate dsRNA. Both replicative and naked IIV-6 genomes trigger production of dsRNA in Drosophila cells, implying direct sensing of invading DNA. Loquacious-PD, a Dicer-2 co-factor essential for the biogenesis of endogenous siRNAs, is dispensable for processing of IIV-6-derived dsRNAs, which suggests that they are distinct. Consistent with this finding, inhibition of the RNAPII co-factor P-TEFb affects the synthesis of endogenous, but not virus-derived, dsRNA. Altogether, our results suggest that a non-canonical RNAPII complex recognizes invading viral DNA to synthesize virus-derived dsRNA, which activates the antiviral siRNA pathway in Drosophila.",
keywords = "CP: Immunology, DNA sensing, antiviral RNAi, dsRNA, invertebrate immunity",
author = "{de Faria}, {Isaque J.S.} and Aguiar, {Eric R.G.R.} and Olmo, {Roenick P.} and {Alves da Silva}, Juliana and Laurent Daeffler and Carthew, {Richard W.} and Imler, {Jean Luc} and Marques, {Jo{\~a}o T.}",
note = "Funding Information: We would like to thank all members of the Marques and Imler laboratories for invaluable assistance and discussions. We also thank Phillip D. Zamore for mutant flies, the Sequencing Platform of Strasbourg (University of Strasbourg) for high-throughput sequencing, and the UFMG microscopy facility (CAPI) for image acquisition. This work of the Interdisciplinary Thematic Institute IMCBio , as part of the ITI 2021-2028 program of the University of Strasbourg , CNRS , and Inserm , was supported by IdEx Unistra ( ANR-10-IDEX-0002 ), by the SFRI-STRAT{\textquoteright}US project ( ANR 20-SFRI-0012 ), and by EUR IMCBio ( IMCBio ANR-17-EURE-0023 ) under the framework of the French Investments for the Future Program as well as by the previous Labex NetRNA ( ANR-10-LABX-0036 ). This work has also been supported by grants from the Conselho Nacional de Desenvolvimento Cient{\'i}fico e Tecnol{\'o}gico , Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de Minas Gerais , Rede Mineira de Imunobiol{\'o}gicos (grant REDE-00140-16 ), Rede Mineira de Biomol{\'e}culas (grant REDE-00125-16 ), Instituto Nacional de Ci{\^e}ncia e Tecnologia de Vacinas (INCTV) , Institute for Advanced Studies of the University of Strasbourg (USIAS Fellowship 2019), and Fonds r{\'e}gionale de coop{\'e}ration pour la recherche FRCT2020 R{\'e}gion Grand-Est (ViroMod) to J.T.M. This study was financed in part by the Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de N{\'i}vel Superior -Brasil (CAPES) - Finance Code 001 to J.T.M. I.S.J.F. was supported by fellowships from CNPq and CAPES . R.W.C. was supported by the NIH ( R35GM118144 ). Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = jun,
day = "21",
doi = "10.1016/j.celrep.2022.110976",
language = "English (US)",
volume = "39",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",
}