Dicer-2-Dependent Generation of Viral DNA from Defective Genomes of RNA Viruses Modulates Antiviral Immunity in Insects

The RNAi pathway confers antiviral immunity in insects. Virus-specific siRNA responses are amplified via the reverse transcription of viral RNA to viral DNA (vDNA). The nature, biogenesis, and regulation of vDNA are unclear. We find that vDNA produced during RNA virus infection of Drosophila and mos...

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Veröffentlicht in:Cell host & microbe 2018-03, Vol.23 (3), p.353-365.e8
Hauptverfasser: Poirier, Enzo Z., Goic, Bertsy, Tomé-Poderti, Lorena, Frangeul, Lionel, Boussier, Jérémy, Gausson, Valérie, Blanc, Hervé, Vallet, Thomas, Loyd, Hyelee, Levi, Laura I., Lanciano, Sophie, Baron, Chloé, Merkling, Sarah H., Lambrechts, Louis, Mirouze, Marie, Carpenter, Susan, Vignuzzi, Marco, Saleh, Maria-Carla
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container_end_page 365.e8
container_issue 3
container_start_page 353
container_title Cell host & microbe
container_volume 23
creator Poirier, Enzo Z.
Goic, Bertsy
Tomé-Poderti, Lorena
Frangeul, Lionel
Boussier, Jérémy
Gausson, Valérie
Blanc, Hervé
Vallet, Thomas
Loyd, Hyelee
Levi, Laura I.
Lanciano, Sophie
Baron, Chloé
Merkling, Sarah H.
Lambrechts, Louis
Mirouze, Marie
Carpenter, Susan
Vignuzzi, Marco
Saleh, Maria-Carla
description The RNAi pathway confers antiviral immunity in insects. Virus-specific siRNA responses are amplified via the reverse transcription of viral RNA to viral DNA (vDNA). The nature, biogenesis, and regulation of vDNA are unclear. We find that vDNA produced during RNA virus infection of Drosophila and mosquitoes is present in both linear and circular forms. Circular vDNA (cvDNA) is sufficient to produce siRNAs that confer partially protective immunity when challenged with a cognate virus. cvDNAs bear homology to defective viral genomes (DVGs), and DVGs serve as templates for vDNA and cvDNA synthesis. Accordingly, DVGs promote the amplification of vDNA-mediated antiviral RNAi responses in infected Drosophila. Furthermore, vDNA synthesis is regulated by the DExD/H helicase domain of Dicer-2 in a mechanism distinct from its role in siRNA generation. We suggest that, analogous to mammalian RIG-I-like receptors, Dicer-2 functions like a pattern recognition receptor for DVGs to modulate antiviral immunity in insects. [Display omitted] •Circular viral DNAs (vDNAs) produced during RNA virus infection are a source of siRNAs•Defective viral genomes (DVG) serve as templates for vDNA synthesis•The helicase domain of Dicer-2 modulates vDNA production and virus persistence•DVGs serve to amplify siRNA-mediated antiviral immunity in insects Poirier et al. show that during RNA virus infection of insects, circular viral DNA is produced, regulated by Dicer-2 helicase domain. The main template for viral DNA is defective viral genomes, which appear to be key viral products modulating the host immune response and the establishment of viral persistence.
doi_str_mv 10.1016/j.chom.2018.02.001
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Virus-specific siRNA responses are amplified via the reverse transcription of viral RNA to viral DNA (vDNA). The nature, biogenesis, and regulation of vDNA are unclear. We find that vDNA produced during RNA virus infection of Drosophila and mosquitoes is present in both linear and circular forms. Circular vDNA (cvDNA) is sufficient to produce siRNAs that confer partially protective immunity when challenged with a cognate virus. cvDNAs bear homology to defective viral genomes (DVGs), and DVGs serve as templates for vDNA and cvDNA synthesis. Accordingly, DVGs promote the amplification of vDNA-mediated antiviral RNAi responses in infected Drosophila. Furthermore, vDNA synthesis is regulated by the DExD/H helicase domain of Dicer-2 in a mechanism distinct from its role in siRNA generation. We suggest that, analogous to mammalian RIG-I-like receptors, Dicer-2 functions like a pattern recognition receptor for DVGs to modulate antiviral immunity in insects. [Display omitted] •Circular viral DNAs (vDNAs) produced during RNA virus infection are a source of siRNAs•Defective viral genomes (DVG) serve as templates for vDNA synthesis•The helicase domain of Dicer-2 modulates vDNA production and virus persistence•DVGs serve to amplify siRNA-mediated antiviral immunity in insects Poirier et al. show that during RNA virus infection of insects, circular viral DNA is produced, regulated by Dicer-2 helicase domain. 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Virus-specific siRNA responses are amplified via the reverse transcription of viral RNA to viral DNA (vDNA). The nature, biogenesis, and regulation of vDNA are unclear. We find that vDNA produced during RNA virus infection of Drosophila and mosquitoes is present in both linear and circular forms. Circular vDNA (cvDNA) is sufficient to produce siRNAs that confer partially protective immunity when challenged with a cognate virus. cvDNAs bear homology to defective viral genomes (DVGs), and DVGs serve as templates for vDNA and cvDNA synthesis. Accordingly, DVGs promote the amplification of vDNA-mediated antiviral RNAi responses in infected Drosophila. Furthermore, vDNA synthesis is regulated by the DExD/H helicase domain of Dicer-2 in a mechanism distinct from its role in siRNA generation. We suggest that, analogous to mammalian RIG-I-like receptors, Dicer-2 functions like a pattern recognition receptor for DVGs to modulate antiviral immunity in insects. [Display omitted] •Circular viral DNAs (vDNAs) produced during RNA virus infection are a source of siRNAs•Defective viral genomes (DVG) serve as templates for vDNA synthesis•The helicase domain of Dicer-2 modulates vDNA production and virus persistence•DVGs serve to amplify siRNA-mediated antiviral immunity in insects Poirier et al. show that during RNA virus infection of insects, circular viral DNA is produced, regulated by Dicer-2 helicase domain. The main template for viral DNA is defective viral genomes, which appear to be key viral products modulating the host immune response and the establishment of viral persistence.</description><subject>Animals</subject><subject>Antiviral Agents</subject><subject>arbovirus</subject><subject>Arboviruses</subject><subject>Arboviruses - immunology</subject><subject>Arboviruses - pathogenicity</subject><subject>Biochemistry, Molecular Biology</subject><subject>circular viral DNA</subject><subject>Culicidae</subject><subject>Culicidae - immunology</subject><subject>DEAD-box RNA Helicases</subject><subject>DEAD-box RNA Helicases - metabolism</subject><subject>defective viral genomes</subject><subject>Dicer-2</subject><subject>DNA, Viral</subject><subject>DNA, Viral - metabolism</subject><subject>Drosophila</subject><subject>Drosophila - immunology</subject><subject>Drosophila Proteins</subject><subject>Drosophila Proteins - genetics</subject><subject>Drosophila Proteins - metabolism</subject><subject>Genes, Viral</subject><subject>Genes, Viral - genetics</subject><subject>Genome, Viral</subject><subject>Genomics</subject><subject>Host-Pathogen Interactions</subject><subject>Host-Pathogen Interactions - genetics</subject><subject>Host-Pathogen Interactions - immunology</subject><subject>Immunology</subject><subject>insect</subject><subject>Life Sciences</subject><subject>Microbiology and Parasitology</subject><subject>Molecular biology</subject><subject>persistence</subject><subject>Point Mutation</subject><subject>Ribonuclease III</subject><subject>Ribonuclease III - genetics</subject><subject>Ribonuclease III - metabolism</subject><subject>RNA Helicases</subject><subject>RNA Helicases - genetics</subject><subject>RNA Helicases - metabolism</subject><subject>RNA Interference</subject><subject>RNA Interference - immunology</subject><subject>RNA virus</subject><subject>RNA Virus Infections</subject><subject>RNA Viruses</subject><subject>RNA Viruses - genetics</subject><subject>RNA Viruses - immunology</subject><subject>RNA Viruses - pathogenicity</subject><subject>RNA, Small Interfering</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Viral</subject><subject>RNA, Viral - metabolism</subject><subject>RNAi</subject><subject>Viral Load</subject><subject>Virology</subject><subject>Virus Replication</subject><issn>1931-3128</issn><issn>1934-6069</issn><issn>1934-6069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFv1DAQhSMEoqXwBzigHLkkjJ04iSWEtOpCu9ICEgKuluNMWK8Se7GTrfrvmXRLBRw4eSx_79nPL0leMsgZsOrNPjc7P-YcWJMDzwHYo-ScyaLMKqjk47uZZQXjzVnyLMY9gBBQs6fJGZcCCtbAeXKztgZDxrM1HtB16Kb0Ch0GPVnvUt-n323QQ7r-tEr74Md0jT2ayR5xwfyIcWG-0Clxc6TtR9_Ng55oWjni7tSbcZydnW5T69KNi2QQnydPej1EfHG_XiTfPrz_enmdbT9fbS5X28wIIaes7ShK24oKAcq2lch5YaRoSlMARSj7hknWG6FBF2Vdt2Un-7LsUZQAFaub4iJ5d_I9zO2InaGA9CJ1CHbU4VZ5bdXfJ87u1A9_VKIRNZdABtnJYPeP7Hq1VQcdJ5yDAiYFFwU7MuJf318Y_M8Z46RGGw0Og3bo56ioLWgKSTkI5SfUBB9jwP7Bn4FaGlZ7tTS8aBoFXFHDJHr1Z6AHye9KCXh7ApC-9WgxqGgsOoOdDfTzqvP2f_6_AEQMt14</recordid><startdate>20180314</startdate><enddate>20180314</enddate><creator>Poirier, Enzo Z.</creator><creator>Goic, Bertsy</creator><creator>Tomé-Poderti, Lorena</creator><creator>Frangeul, Lionel</creator><creator>Boussier, Jérémy</creator><creator>Gausson, Valérie</creator><creator>Blanc, Hervé</creator><creator>Vallet, Thomas</creator><creator>Loyd, Hyelee</creator><creator>Levi, Laura I.</creator><creator>Lanciano, Sophie</creator><creator>Baron, Chloé</creator><creator>Merkling, Sarah H.</creator><creator>Lambrechts, Louis</creator><creator>Mirouze, Marie</creator><creator>Carpenter, Susan</creator><creator>Vignuzzi, Marco</creator><creator>Saleh, Maria-Carla</creator><general>Elsevier Inc</general><general>Elsevier</general><general>Cell Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8593-4117</orcidid><orcidid>https://orcid.org/0000-0002-2249-377X</orcidid><orcidid>https://orcid.org/0000-0002-6823-4474</orcidid><orcidid>https://orcid.org/0000-0001-5958-2138</orcidid><orcidid>https://orcid.org/0000-0002-0992-8775</orcidid><orcidid>https://orcid.org/0000-0002-9727-3448</orcidid><orcidid>https://orcid.org/0000-0002-0514-1270</orcidid></search><sort><creationdate>20180314</creationdate><title>Dicer-2-Dependent Generation of Viral DNA from Defective Genomes of RNA Viruses Modulates Antiviral Immunity in Insects</title><author>Poirier, Enzo Z. ; Goic, Bertsy ; Tomé-Poderti, Lorena ; Frangeul, Lionel ; Boussier, Jérémy ; Gausson, Valérie ; Blanc, Hervé ; Vallet, Thomas ; Loyd, Hyelee ; Levi, Laura I. ; Lanciano, Sophie ; Baron, Chloé ; Merkling, Sarah H. ; Lambrechts, Louis ; Mirouze, Marie ; Carpenter, Susan ; Vignuzzi, Marco ; Saleh, Maria-Carla</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c559t-bd606bb56e004bb9e223c9584c305034f8191fc5a0a3477b4d9f44fe540061783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Antiviral Agents</topic><topic>arbovirus</topic><topic>Arboviruses</topic><topic>Arboviruses - immunology</topic><topic>Arboviruses - pathogenicity</topic><topic>Biochemistry, Molecular Biology</topic><topic>circular viral DNA</topic><topic>Culicidae</topic><topic>Culicidae - immunology</topic><topic>DEAD-box RNA Helicases</topic><topic>DEAD-box RNA Helicases - metabolism</topic><topic>defective viral genomes</topic><topic>Dicer-2</topic><topic>DNA, Viral</topic><topic>DNA, Viral - metabolism</topic><topic>Drosophila</topic><topic>Drosophila - immunology</topic><topic>Drosophila Proteins</topic><topic>Drosophila Proteins - genetics</topic><topic>Drosophila Proteins - metabolism</topic><topic>Genes, Viral</topic><topic>Genes, Viral - genetics</topic><topic>Genome, Viral</topic><topic>Genomics</topic><topic>Host-Pathogen Interactions</topic><topic>Host-Pathogen Interactions - genetics</topic><topic>Host-Pathogen Interactions - immunology</topic><topic>Immunology</topic><topic>insect</topic><topic>Life Sciences</topic><topic>Microbiology and Parasitology</topic><topic>Molecular biology</topic><topic>persistence</topic><topic>Point Mutation</topic><topic>Ribonuclease III</topic><topic>Ribonuclease III - genetics</topic><topic>Ribonuclease III - metabolism</topic><topic>RNA Helicases</topic><topic>RNA Helicases - genetics</topic><topic>RNA Helicases - metabolism</topic><topic>RNA Interference</topic><topic>RNA Interference - immunology</topic><topic>RNA virus</topic><topic>RNA Virus Infections</topic><topic>RNA Viruses</topic><topic>RNA Viruses - genetics</topic><topic>RNA Viruses - immunology</topic><topic>RNA Viruses - pathogenicity</topic><topic>RNA, Small Interfering</topic><topic>RNA, Small Interfering - genetics</topic><topic>RNA, Viral</topic><topic>RNA, Viral - metabolism</topic><topic>RNAi</topic><topic>Viral Load</topic><topic>Virology</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Poirier, Enzo Z.</creatorcontrib><creatorcontrib>Goic, Bertsy</creatorcontrib><creatorcontrib>Tomé-Poderti, Lorena</creatorcontrib><creatorcontrib>Frangeul, Lionel</creatorcontrib><creatorcontrib>Boussier, Jérémy</creatorcontrib><creatorcontrib>Gausson, Valérie</creatorcontrib><creatorcontrib>Blanc, Hervé</creatorcontrib><creatorcontrib>Vallet, Thomas</creatorcontrib><creatorcontrib>Loyd, Hyelee</creatorcontrib><creatorcontrib>Levi, Laura I.</creatorcontrib><creatorcontrib>Lanciano, Sophie</creatorcontrib><creatorcontrib>Baron, Chloé</creatorcontrib><creatorcontrib>Merkling, Sarah H.</creatorcontrib><creatorcontrib>Lambrechts, Louis</creatorcontrib><creatorcontrib>Mirouze, Marie</creatorcontrib><creatorcontrib>Carpenter, Susan</creatorcontrib><creatorcontrib>Vignuzzi, Marco</creatorcontrib><creatorcontrib>Saleh, Maria-Carla</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell host &amp; microbe</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Poirier, Enzo Z.</au><au>Goic, Bertsy</au><au>Tomé-Poderti, Lorena</au><au>Frangeul, Lionel</au><au>Boussier, Jérémy</au><au>Gausson, Valérie</au><au>Blanc, Hervé</au><au>Vallet, Thomas</au><au>Loyd, Hyelee</au><au>Levi, Laura I.</au><au>Lanciano, Sophie</au><au>Baron, Chloé</au><au>Merkling, Sarah H.</au><au>Lambrechts, Louis</au><au>Mirouze, Marie</au><au>Carpenter, Susan</au><au>Vignuzzi, Marco</au><au>Saleh, Maria-Carla</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dicer-2-Dependent Generation of Viral DNA from Defective Genomes of RNA Viruses Modulates Antiviral Immunity in Insects</atitle><jtitle>Cell host &amp; microbe</jtitle><addtitle>Cell Host Microbe</addtitle><date>2018-03-14</date><risdate>2018</risdate><volume>23</volume><issue>3</issue><spage>353</spage><epage>365.e8</epage><pages>353-365.e8</pages><issn>1931-3128</issn><issn>1934-6069</issn><eissn>1934-6069</eissn><abstract>The RNAi pathway confers antiviral immunity in insects. Virus-specific siRNA responses are amplified via the reverse transcription of viral RNA to viral DNA (vDNA). The nature, biogenesis, and regulation of vDNA are unclear. We find that vDNA produced during RNA virus infection of Drosophila and mosquitoes is present in both linear and circular forms. Circular vDNA (cvDNA) is sufficient to produce siRNAs that confer partially protective immunity when challenged with a cognate virus. cvDNAs bear homology to defective viral genomes (DVGs), and DVGs serve as templates for vDNA and cvDNA synthesis. Accordingly, DVGs promote the amplification of vDNA-mediated antiviral RNAi responses in infected Drosophila. Furthermore, vDNA synthesis is regulated by the DExD/H helicase domain of Dicer-2 in a mechanism distinct from its role in siRNA generation. We suggest that, analogous to mammalian RIG-I-like receptors, Dicer-2 functions like a pattern recognition receptor for DVGs to modulate antiviral immunity in insects. [Display omitted] •Circular viral DNAs (vDNAs) produced during RNA virus infection are a source of siRNAs•Defective viral genomes (DVG) serve as templates for vDNA synthesis•The helicase domain of Dicer-2 modulates vDNA production and virus persistence•DVGs serve to amplify siRNA-mediated antiviral immunity in insects Poirier et al. show that during RNA virus infection of insects, circular viral DNA is produced, regulated by Dicer-2 helicase domain. The main template for viral DNA is defective viral genomes, which appear to be key viral products modulating the host immune response and the establishment of viral persistence.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29503180</pmid><doi>10.1016/j.chom.2018.02.001</doi><orcidid>https://orcid.org/0000-0001-8593-4117</orcidid><orcidid>https://orcid.org/0000-0002-2249-377X</orcidid><orcidid>https://orcid.org/0000-0002-6823-4474</orcidid><orcidid>https://orcid.org/0000-0001-5958-2138</orcidid><orcidid>https://orcid.org/0000-0002-0992-8775</orcidid><orcidid>https://orcid.org/0000-0002-9727-3448</orcidid><orcidid>https://orcid.org/0000-0002-0514-1270</orcidid><oa>free_for_read</oa></addata></record>
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source MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects Animals
Antiviral Agents
arbovirus
Arboviruses
Arboviruses - immunology
Arboviruses - pathogenicity
Biochemistry, Molecular Biology
circular viral DNA
Culicidae
Culicidae - immunology
DEAD-box RNA Helicases
DEAD-box RNA Helicases - metabolism
defective viral genomes
Dicer-2
DNA, Viral
DNA, Viral - metabolism
Drosophila
Drosophila - immunology
Drosophila Proteins
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Genes, Viral
Genes, Viral - genetics
Genome, Viral
Genomics
Host-Pathogen Interactions
Host-Pathogen Interactions - genetics
Host-Pathogen Interactions - immunology
Immunology
insect
Life Sciences
Microbiology and Parasitology
Molecular biology
persistence
Point Mutation
Ribonuclease III
Ribonuclease III - genetics
Ribonuclease III - metabolism
RNA Helicases
RNA Helicases - genetics
RNA Helicases - metabolism
RNA Interference
RNA Interference - immunology
RNA virus
RNA Virus Infections
RNA Viruses
RNA Viruses - genetics
RNA Viruses - immunology
RNA Viruses - pathogenicity
RNA, Small Interfering
RNA, Small Interfering - genetics
RNA, Viral
RNA, Viral - metabolism
RNAi
Viral Load
Virology
Virus Replication
title Dicer-2-Dependent Generation of Viral DNA from Defective Genomes of RNA Viruses Modulates Antiviral Immunity in Insects
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