title: Circulating Immune Cells Mediate a Systemic RNAi-Based Adaptive Antiviral Response in Drosophila.
abstract: Effective antiviral protection in multicellular organisms relies on both cell-autonomous and systemic immunity. Systemic immunity mediates the spread of antiviral signals from infection sites to distant uninfected tissues. In arthropods, RNA interference (RNAi) is responsible for antiviral defense. Here, we show that flies have a sophisticated systemic RNAi-based immunity mediated by macrophage-like haemocytes. Haemocytes take up dsRNA from infected cells and, through endogenous transposon reverse transcriptases, produce virus-derived complementary DNAs (vDNA). These vDNAs template de novo synthesis of secondary viral siRNAs (vsRNA), which are secreted in exosome-like vesicles. Strikingly, exosomes containing vsRNAs, purified from haemolymph of infected flies, confer passive protection against virus challenge in naive animals. Thus, similar to vertebrates, insects use immune cells to generate immunological memory in the form of stable vDNAs that generate systemic immunity, which is mediated by the vsRNA-containing exosomes.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94122-2280, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Tassetto
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94122-2280, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Kunitomi
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94122-2280, USA. Electronic address: raul.andino@ucsf.edu.
authors.forename: Raul
authors.initials: R
authors.lastname: Andino
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D055354:Exosomes / Q000378:metabolism; D006434:Hemocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D007156:Immunologic Memory; D034622:RNA Interference; D012367:RNA, Viral / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D048348:Reverse Transcription / Q000187:drug effects; D012845:Sindbis Virus / Q000235:genetics / Q000502:physiology*; D015215:Zidovudine / Q000494:pharmacology
chemical_list: C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine