Natural Variation in Resistance to Virus Infection in Dipteran Insects

Abstract

The power and ease of Drosophila genetics and the medical relevance of mosquito-transmitted viruses have made dipterans important model organisms in antiviral immunology. Studies of virus–host interactions at the molecular and population levels have illuminated determinants of resistance to virus infection. Here, we review the sources and nature of variation in antiviral immunity and virus susceptibility in model dipteran insects, specifically the fruit fly Drosophila melanogaster and vector mosquitoes of the genera Aedes and Culex. We first discuss antiviral immune mechanisms and describe the virus-specificity of these responses. In the following sections, we review genetic and microbiota-dependent variation in antiviral immunity. In the final sections, we explore less well-studied sources of variation, including abiotic factors, sexual dimorphism, infection history, and endogenous viral elements. We borrow from work on other pathogen types and non-dipteran species when it parallels or complements studies in dipterans. Understanding natural variation in virus–host interactions may lead to the identification of novel restriction factors and immune mechanisms and shed light on the molecular determinants of vector competence.

Endogenous viral elements are widespread in arthropod genomes and commonly give rise to piRNAs

“…RNA interference (RNAi) is the primary antiviral mechanism in arthropods and relies on three classes of small RNAs (sRNAs) [6, 7]. The small interfering RNA (siRNA) pathway is the most important branch of RNAi for combating viral infection in arthropods and this pathway relies on the production of primarily 21 nt siRNAs via cleavage of viral double-stranded RNA [7].…”

Induction and suppression of NF-kB signalling by a DNA virus ofDrosophila

“…For RNAi mutants, flies were also assayed at 3 dpi. DNA was extracted by phenol-chloroform precipitation and viral titre estimated by quantitative PCR relative to host genomic DNA, using previously described primers (rpl32; Palmer et al, 2018)). Log-transformed viral titre was analysed as a Gaussian response variable using MCMCglmm (Hadfield, 2010), with genotype, dpi, and genotype-by-dpi interactions as fixed effects.…”

“…Antiviral immune mechanisms that target RNA viruses include RNAmediated defences such as RNA interference (RNAi) and RNA decay pathways, cellular defences such as apoptosis, phagocytosis, and autophagy, and transcriptional responses. The latter are primarily mediated by Janus kinase/signal transducers and activators of transcription (JAK-STAT) and Nuclear factor κB (NF-κB) pathways (reviewed in Merkling and van Rij, 2013;Bronkhorst and van Rij, 2014;Lamiable and Imler, 2014;Xu and Cherry, 2014;Palmer, Varghese and van Rij, 2018).…”

“…There are two NF-κB pathways in Drosophila: Toll and Imd, which primarily function in antibacterial (Toll: gram-positive, Imd: gram-negative) and antifungal (Toll) defense, although both provide protection against some RNA viruses (reviewed in Valanne, Wang and Ramet, 2011;Merkling and van Rij, 2013;Lamiable and Imler, 2014;Myllymaki, Valanne and Ramet, 2014;Palmer, Varghese and of Toll signalling has no effect on virus replication. Through re-analysis of previous RNA-sequencing data, we observe a broad downregulation of NF-κB responsive antimicrobial peptides following infection, and perform a small-scale screen for KV-encoded immune inhibitors.…”

Variation in host susceptibility to different pathogens: an experimental and phylogenetic study of Drosophila-viruses

“…Hosts have evolved diverse adaptations to avoid pathogen infection and replication, ranging from complex antiviral innate immune pathways in dipteran insects (Palmer et al, 2018) to behaviours that reduce the probability of encounter between host and parasite (Theimann & Wassersug, 2000). Despite some isolate cases where defence seems not to be costly (Heath et al, 2017), these strategies consume resources which the host could use to perform other activities (Sheldon & Verhulst, 1996).…”