Specificity of resistance to dengue virus isolates is associated with genotypes of the mosquito antiviral geneDicer-2

Abstract

In contrast to the prevailing view that invertebrate immunity relies on broad-spectrum recognition and effector mechanisms, intrinsic genetic compatibility between invertebrate hosts and their pathogens is often highly specific in nature. Solving this puzzle requires a better understanding of the molecular basis underlying observed patterns of invertebrate host–pathogen genetic specificity, broadly referred to as genotype-by-genotype interactions. Here, we identify an invertebrate immune gene in which natural polymorphism is associated with isolate-specific resistance to an RNA virus.Dicer-2(dcr2) encodes a key protein upstream of the RNA interference (RNAi) pathway, a major antiviral component of innate immunity in invertebrates. We surveyed allelic polymorphism at thedcr2locus in a wild-type outbred population and in three derived isofemale families of the mosquitoAedes aegyptithat were experimentally exposed to several, genetically distinct isolates of dengue virus. We found thatdcr2genotype was associated with resistance to dengue virus in a virus isolate-specific manner. By contrast, no such association was found for genotypes at two control loci flankingdcr2, making it likely thatdcr2contains the yet-unidentified causal polymorphism(s). This result supports the idea that host–pathogen compatibility in this system depends, in part, on a genotype-by-genotype interaction betweendcr2and the viral genome, and points to the RNAi pathway as a potentially important determinant of intrinsic insect-virus genetic specificity.