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.

Highlights

  • The vast majority of research on invertebrate antiviral immunity has used dipteran systems, including the fruit fly Drosophila and the medically important vector mosquitoes of the genera Culex, Aedes, and Anopheles

  • We provide a general description of antiviral immune mechanisms, and their impact across virus species studied in dipterans

  • The antiviral role of JAK-STAT signaling has been investigated across Drosophila viruses, where it is crucial in Cricket paralysis virus (CrPV) and DCV infections, but exerts a minimal effect on Flock House virus (FHV), Sindbis virus (SINV) and vesicular stomatitis virus (VSV) [21,71]

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Summary

Introduction

The vast majority of research on invertebrate antiviral immunity has used dipteran systems, including the fruit fly Drosophila and the medically important vector mosquitoes of the genera Culex, Aedes, and Anopheles. The comparison of antiviral processes in these dipterans highlights a conserved yet dynamic immune system, with some antiviral mechanisms conserved from flies to mammals, whereas others have evolved since the expansion of dipterans Studies from both fruit flies and mosquitoes have uncovered variation in host–virus interactions. Variation in resistance is further complicated in mosquitoes, where the phenotype of interest is vector competence, the ability of a mosquito to transmit an arbovirus after it had crossed multiple infection barriers (midgut infection barrier (MIB), midgut escape barrier (MEB), salivary gland infection barrier, and salivary gland escape barrier) (reviewed in [8]) Viral genetic variation, both within and between hosts, is likely to contribute to infection outcomes [9,10]. For a list of viruses discussed in this review, see Table 1

Antiviral Immune Processes
RNA Interference
Other RNA Processes
Nuclear Factor κB Pathways
JAK-STAT Pathway
Nutrient Signaling
Virus-Specific Responses
Induced Immune Responses
Genetic Variation in Antiviral Immunity in Dipterans
Segregating Genetic Variants Associated with Viral Resistance in Drosophila
Evolution of Resistance Loci
Genetic Variation Associated with Viral Resistance in Mosquitoes
Microbe-Dependent Variation in Dipteran Antiviral Immunity
Wolbachia in Drosophila
Wolbachia in Mosquitoes
Gut Microbiota in Drosophila
Gut Microbiota in Mosquitoes
Other Sources of Variation
Abiotic Environment
Sexual Dimorphism and Mating
Infection History
Endogenous Viral Elements—Non-Retroviral Integrated RNA Virus Sequences
Findings
Concluding Remarks
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