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.
Aliyari
Roghiyh
R
Department of Plant Pathology and Microbiology, Institute for Integrative Genome Biology, University of California, Riverside, Riverside, CA 92521, USA.
Wu
Qingfa
Q
Li
Hong-Wei
HW
Wang
Xiao-Hong
XH
Li
Feng
F
Green
Lance D
LD
Han
Cliff S
CS
Li
Wan-Xiang
WX
Ding
Shou-Wei
SW
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