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Evidence for ADAR-induced Hypermutation of the Drosophila Sigma Virus (Rhabdoviridae)

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Evidence for ADAR-induced Hypermutation of the Drosophila Sigma Virus (Rhabdoviridae)

Jennifer A Carpenter et al. BMC Genet.

Abstract

Background: ADARs are RNA editing enzymes that target double stranded RNA and convert adenosine to inosine, which is read by translation machinery as if it were guanosine. Aside from their role in generating protein diversity in the central nervous system, ADARs have been implicated in the hypermutation of some RNA viruses, although why this hypermutation occurs is not well understood.

Results: Here we describe the hypermutation of adenosines to guanosines in the genome of the sigma virus--a negative sense RNA virus that infects Drosophila melanogaster. The clustering of these mutations and the context in which they occur indicates that they have been caused by ADARs. However, ADAR-editing of viral RNA is either rare or edited viral RNA are rapidly degraded, as we only detected evidence for editing in two of the 104 viral isolates we studied.

Conclusion: This is the first evidence for ADARs targeting viruses outside of mammals, and it raises the possibility that ADARs could play a role in the antiviral defences of insects.

Figures

Figure 1
Figure 1
Sequences of the gene encoding the PP3 protein of sigma virus that contain clusters of A to G mutations. The sequences are shown in positive sense (the mRNA sequence rather than the genome sequence). (a) Isolates A3 and A3 E55 (2'916 - 2'316). These were laboratory maintained lines that were split from each other ~15 years ago. (b) The field isolate DM113 (3'194 - 2'954). (c) The field isolate U125 (2'693 - 2'574). (d) The field isolate Derby (3'074 - 2'954). This isolate was polymorphic for five A to G changes in the PP3 protein (these ambiguous bases are indicated by the wobble code R). In all the panels, sites that have not been mutated are represented by a period and the ancestral sequences were reconstructed by parsimony using a phylogeny of the viral sequences. The nucleotide locations refer to the position in negative sense genome of Genbank accession AM689308 (isolate A3).
Figure 2
Figure 2
Proportion of edited transcripts in two genes (Graph A: Nicotinic Acetylcholine Receptor a 34E (nAChR); Graph B: Resistant to dieldrin (Rdl) in Drosophila either infected with the sigma virus or uninfected. nAChR is edited at 10 sites, Rdl is edited at 6. Graphs show means with standard errors.

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