Wolbachia Variants Induce Differential Protection to Viruses in Drosophila melanogaster: A Phenotypic and Phylogenomic Analysis

Abstract

Wolbachia are intracellular bacterial symbionts that are able to protect various insect hosts from viral infections. This tripartite interaction was initially described in Drosophila melanogaster carrying wMel, its natural Wolbachia strain. wMel has been shown to be genetically polymorphic and there has been a recent change in variant frequencies in natural populations. We have compared the antiviral protection conferred by different wMel variants, their titres and influence on host longevity, in a genetically identical D. melanogaster host. The phenotypes cluster the variants into two groups — wMelCS-like and wMel-like. wMelCS-like variants give stronger protection against Drosophila C virus and Flock House virus, reach higher titres and often shorten the host lifespan. We have sequenced and assembled the genomes of these Wolbachia, and shown that the two phenotypic groups are two monophyletic groups. We have also analysed a virulent and over-replicating variant, wMelPop, which protects D. melanogaster even better than the closely related wMelCS. We have found that a ∼21 kb region of the genome, encoding eight genes, is amplified seven times in wMelPop and may be the cause of its phenotypes. Our results indicate that the more protective wMelCS-like variants, which sometimes have a cost, were replaced by the less protective but more benign wMel-like variants. This has resulted in a recent reduction in virus resistance in D. melanogaster in natural populations worldwide. Our work helps to understand the natural variation in wMel and its evolutionary dynamics, and inform the use of Wolbachia in arthropod-borne disease control.

Author Summary

Wolbachia are bacterial symbionts that infect many arthropods and can protect insects from viral infection. Here we show that different variants of Wolbachia from Drosophila melanogaster (wMel) are phenotypically heterogeneous: they differ in the level of protection they confer and the titres they reach in their host. The Wolbachia with higher titres have higher antiviral protection but can also exert a cost on their host. Based on the observed phenotypes, we divided the wMel variants into two groups and demonstrated that the division is reflected in their phylogeny. Moreover, we discovered the genetic difference between two otherwise almost identical wMel variants, wMelPop and wMelCS, that may explain why one is highly pathogenic while the other produces benign infections. Our study helps to explain the prevalence of the different wMel variants in wild Drosophila populations and sheds light on the factors shaping it. In particular, the recent replacement of some wMel variants caused a decrease in anti-viral resistance and probably reduced the cost of the symbiont for the host. Finally, our work helps to understand the interaction of wMel with its natural host and inform Wolbachia use in the control of diseases transmitted by insects.