Vector-borne pathogens frequently modify traits of their primary hosts and vectors in ways that influence disease transmission. Such effects can themselves be altered by the presence of other microbial symbionts, yet we currently have limited understanding of these interactions. Here we show that effects of pea enation mosaic virus (PEMV) on interactions between host plants and aphid vectors are modulated by the presence of different aphid endosymbionts. In a series of laboratory assays, we found strong interactive effects of virus infection and endosymbionts on aphid metabolomic profiles, population growth, behavior, and virus transmission during aphid feeding. Furthermore, the strongest effects—and those predicted to favor virus transmission—were most apparent in aphid lines harboring particular endosymbionts. These findings show that virus effects on host-vector interactions can be strongly influenced by other microbial symbionts and suggest a potentially important role for such interactions in disease ecology and evolution.
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