Abstract Plants defend themselves from viral infection using RNA interference (RNAi), an evolutionarily conserved mechanism that degrades viral RNA through the production of small interfering RNAs. As a counter defense, plant viruses evolved suppressors of RNA silencing (VSRs) to inhibit plant RNAi machinery, aiding viral replication and transmission. P0, a VSR encoded by the potato leafroll virus (PLRV), family Polerovirus , suppresses RNAi by targeting the plant protein ARGONATE 1 for degradation through its F-box motif interaction with a Skp1 subunit of the family of E3 ubiquitin ligases. Our previous work shows PLRV P0 suppresses antiviral immunity in its aphid vector Myzus persicae , leading to an increase in aphid infection by the insect virus Myzus persicae densovirus (MpDNV). Here, we expand on these findings and show that the P0 protein also regulates aphid fecundity. Using a series of F-box mutants, we demonstrate that a functional P0 F-box motif is required for inhibition MpDNV antiviral immunity but not modulation of aphid fecundity. We further show that silencing suppressors from non-aphid-borne plant viruses that target other components of the plant’s RNAi machinery also modulate aphid fecundity but not MpDNV titer. Collectively, the results show that aphids have been favored by selection to modulate their anti-viral immunity and fecundity in response to changes in the plant RNAi pathways induced by plant viral infection. These data highlight the intricate co-evolution of plant viruses, their vectors, and host defenses. This knowledge may open new avenues for managing vector-borne plant diseases by targeting viral proteins to manipulate insect vectors.