The DExD/H-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila

Abstract

Drosophila, like other invertebrates and plants, relies mainly on RNA interference for its defense against viruses. In flies, viral infection also triggers the expression of many genes. One of the genes induced, Vago, encodes a 18-kilodalton cysteine-rich polypeptide. Here we provide genetic evidence that the Vago gene product controlled viral load in the fat body after infection with drosophila C virus. Induction of Vago was dependent on the helicase Dicer-2. Dicer-2 belongs to the same DExD/H-box helicase family as do the RIG-I-like receptors, which sense viral infection and mediate interferon induction in mammals. We propose that this family represents an evolutionary conserved set of sensors that detect viral nucleic acids and direct antiviral responses.

Dicing of viral replication intermediates during silencing of latent Drosophila viruses

“…However, if the infection can be adequately controlled, the necessity to sort viral siRNAs into RISC might conceivably become less critical, whereas Dicer-2 remains active in turning over the remaining persistent viral RNAs. Dicer-2 was also recently shown to induce the antiviral Vago protein, apparently in an AGO2-independent manner, demonstrating that the role of Dicer-2 extends beyond simply the generation of antiviral RISC (28). Nevertheless, there is clearly a role for AGO2 in suppressing latent FHV (17), as with acute FHV infection (2,5,19).…”

Making connections in insect innate immunity

“…Some of these target genes are associated with phagocytosis (tep1), whereas others have been implicated in the general stress response and hemocyte proliferation (totA and raf, respectively) (14). When specifically considering viral infection, the Jak-STAT pathway has been shown to be activated by and produce an antiviral response to Drosophila C virus, Sindbis virus, WNV, and Dengue virus, among others (10,17,18). Virus infection induces a specific STAT-responsive transcription profile, characterized by increased transcription of previously unidentified genes and negligible change in standard pathway targets identified following bacterial infection in Drosophila (10).…”

“…Virus infection induces a specific STAT-responsive transcription profile, characterized by increased transcription of previously unidentified genes and negligible change in standard pathway targets identified following bacterial infection in Drosophila (10). Specifically, the transcription of the gene vir-1 is highly up-regulated during Drosophila C virus infection of Drosophila, (17). Further investigation determined that vago expression was dependent on Dicer-2 activity in the presence of viral RNA replication, but did not require the other proteins required for the RNAi response (17).…”

“…Specifically, the transcription of the gene vir-1 is highly up-regulated during Drosophila C virus infection of Drosophila, (17). Further investigation determined that vago expression was dependent on Dicer-2 activity in the presence of viral RNA replication, but did not require the other proteins required for the RNAi response (17). This led to the conclusion that Dicer-2 has signaling capabilities in response to dsRNA detection that are independent of the RNAi pathway.…”

Homologous RIG-I–like helicase proteins direct RNAi-mediated antiviral immunity in C. elegans by distinct mechanisms

“…Pathogen sensing by several classes of immune receptors such as retinoic acid inducible gene I (RIG-I)-like cytosolic sensors in mammals leads to the transcriptional activation of effector genes in the nucleus (1). In contrast, detection of viral double-stranded RNA (dsRNA) by Dicer endonucleases is associated with the production of small interfering RNAs (siRNAs), which subsequently direct sequencespecific antiviral immunity through RNA interference (RNAi) (2)(3)(4)(5). Antiviral RNAi is a major antiviral defense mechanism in fungi, plants, insects, and nematodes, so that suppression of the defense by a virus-encoded suppressor of RNAi is essential to establish infection (6)(7)(8).…”