Nora Virus VP4b and ORF1 Circulate in Hemolymph of Infected D. melanogaster with Coordinate Expression of Vago and Vir-1.

Amanda Macke,Darby J Carlson,Wilfredo Lopez,Kimberly A Carlson

doi:10.3390/vaccines8030491

Abstract

Study of the novel RNA virus, Nora virus, which is a persistent, picorna-like virus that replicates in the gut of Drosophila melanogaster offers insight into human innate immunity and other picorna-like viruses. Nora virus infection leads to a locomotor abnormality and upregulation of two candidate target proteins, Vago and Virus-induced RNA 1 (Vir-1). These proteins are uncharacterized in response to Nora virus. We hypothesize that Nora virus is circulating in the hemolymph of Nora virus-infected D. melanogaster, allowing for migration beyond the primary site of replication in the gut. Analysis by qRT-PCR demonstrated biphasic viral load and corresponding vago and vir-1 transcription levels, suggesting transcription of vago and vir-1 occurs in response to viral infection. However, Vir-1 is also present in virus-free D. melanogaster suggesting basal expression or alternative functions. Presence of Nora virus RNA and the Viral Protein 4b (VP4b), in hemolymph of infected D. melanogaster supports the hypothesized circulation of Nora virus in the hemolymph. The study suggests that impaired locomotor function may be due to transport of Nora virus from the gut to the brain via the hemolymph.

Highlights

The Drosophila melanogaster innate immune system shares several characteristics with its mammalian counterparts, including origin, type, and timeframe of the immune response [1]
The current study provides evidence that Nora virus may be circulating in the hemolymph and within the gut tissue of infected D. melanogaster [13]
The increasing vago transcription demonstrated in this study suggests that the RNA interference (RNAi) pathway is still functional in Nora virus-infected D. melanogaster and it is unlikely that Nora virus produces an RNAi inhibitor

Summary

Introduction

The Drosophila melanogaster innate immune system shares several characteristics with its mammalian counterparts, including origin, type, and timeframe of the immune response [1]. Of the genes associated with the innate immune response in D. melanogaster, 77% are shared with humans [2]. For this reason, D. melanogaster provide an manipulated model for many immune pathways and offer novel target proteins for study in disease models. One group of mammalian proteins, the Toll-like receptor family, was first identified in response to a Drosophila protein, Toll, involved in activation of the Nuclear factor-Kappa B (NF-κB) pathway [3]. In D. melanogaster, innate immune responses include autophagy, RNA interference (RNAi), and several pathways including the

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Results

Conclusion