Mechanism of induction and suppression of antiviral immunity directed by virus-derived small RNAs in Drosophila.
The small RNA-directed viral immunity pathway in plants and invertebrates begins with the production by Dicer nuclease of virus-derived siRNAs (viRNAs), which guide specific antiviral silencing by Argonaute protein in an RNA-induced silencing complex (RISC). Molecular identity of the viral RNA precursor of viRNAs remains a matter of debate. Using Flock house virus (FHV) infection of Drosophila as a model, we show that replication of FHV positive-strand RNA genome produces an approximately 400 bp dsRNA from its 5' terminus that serves as the major Dicer-2 substrate. ViRNAs thus generated are loaded in Argonaute-2 and methylated at their 3' ends. Notably, FHV-encoded RNAi suppressor B2 protein interacts with both viral dsRNA and RNA replicase and inhibits production of the 5'-terminal viRNAs. Our findings, therefore, provide a model in which small RNA-directed viral immunity is induced during the initiation of viral progeny (+)RNA synthesis and suppressed by B2 inside the viral RNA replication complex.
Department of Plant Pathology and Microbiology, Institute for Integrative Genome Biology, University of California, Riverside, Riverside, CA 92521, USA.
Roghiyh
R
Aliyari
Qingfa
Q
Wu
Hong-Wei
HW
Li
Xiao-Hong
XH
Wang
Feng
F
Li
Lance D
LD
Green
Cliff S
CS
Han
Wan-Xiang
WX
Li
Shou-Wei
SW
Ding
D000818:Animals; D060565:Argonaute Proteins; D004330:Drosophila / Q000276:immunology* / Q000821:virology*; D029721:Drosophila Proteins / Q000378:metabolism; D020868:Gene Silencing; D008745:Methylation; D008954:Models, Biological; D030381:Nodaviridae / Q000276:immunology*; D020365:RNA Helicases / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012327:RNA Virus Infections / Q000276:immunology*; D012330:RNA, Double-Stranded / Q000276:immunology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000276:immunology* / Q000378:metabolism; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D043244:Ribonuclease III
C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D012367:RNA, Viral; D034743:RNA-Induced Silencing Complex; C478069:DCR-2 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases