The role of ANTi-RVFV Immunity in GermliNe infection and bEhavior modulation in insects (ANTIGoNE)

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Arboviruses are transmitted between vertebrate host and arthropod vectors. Many of these viruses cause neurological defects or abortions in mammalian hosts. However, infection phenotypes in insects are not well characterized. The insect immune response to these arthropod-borne (arbo) viruses is key to keep infected insects sufficiently healthy to enable host finding and production of offspring, two of the major influencing factors for virus transmission. The insects' immune system relies mainly on antiviral RNA interference to combat a larger variety of different viral pathogens. This RNAi mechanism is initiated by the recognition and cleavage of double-stranded (ds) RNA by the RNAseIII enzyme Dicer-2 (Dcr-2) which then leads to degradation of intruding viral genomes by the RNA-induced silencing complex (RISC) including the Argonaute 2 (Ago2) protein. Furthermore, piRNA pathways are active in the germline cells to protect genomes form massive disruption through movement of transposable elements. In the past years, also piRNAs originating from arbovirus genomes were described raising the question of their role in insect’s immune responses. Pi and siRNA responses in germline tissues are of special interest in arbovirus infection since many of those viruses are transmitted vertically within a mosquito population. Especially viruses of the order Bunyavirales are efficiently transmitted through the germline to mosquito offspring without affecting the health of mosquito offspring. In contrast, the transmission of bunyaviruses to the offspring of mammals leads to severe abnormality in fetus development and often results in abortion. This raises the question how insects keep the delicate balance of allowing viral replication and the protection of offspring health to allow transovarial transmission. Furthermore, pathogen infection in mosquitoes can induce behavioral changes; for example Aedes triseriatus mosquitoes infected with La Crosse virus (Bunyaviridae) show a higher probing frequency than uninfected siblings and Zika virus (Flaviviridae) infection on neuronal cells increases neuronal activity in Aedes aegypti. These observations raise the question: By which mechanisms do arboviruses affect neuron function in insects (direct damage to neurons by infection or indirect damage by immune pathway activation).To tackle both questions, we will use the infection models for Rift valley fever virus (Bunyaviridae, RVFV) in the model insect Drosophila melanogaster and measure virus growth in different tissues, immune reaction in germlines and neuronal tissues and behavior in infected individuals by a different behavioral assays and electroantennograms. The proposed studies will help us to analyze adaptive changes in insects host seeking behavior and the underlying molecular mechanisms as well as the role of antiviral pathways in infection of germline cells.