Baculovirus bv/odv-e26 is required for host behavioral manipulation by optimizing viral virulence to lepidopteran hosts

Abstract

Host behavioral manipulation is a widely used strategy for parasites to enhance their transmission. Lepidopteran nucleopolyhedroviruses (NPVs) induce hyperactivity and alteration of behavioral patterns in host insect larvae. Previous studies revealed that Bombyx mori nucleopolyhedrovirus (BmNPV) does not induce hyperactivity in larval Bombyx mori, when Bm8, a homologue of the baculovirus bv/odv-e26 gene, is knocked out. Bm8 knockout also enhances pathogenicity, but the relationship between Bm8 functions and host behavioral manipulation is still unknown. This study revealed that Bm8 is dispensable for altering behavioral patterns but crucial for inducing hyperactivity. Bm8 overexpression decreased pathogenicity in B. mori larvae and delayed viral infection in cultured cells. These results suggest that Bm8 maintains larval locomotory activity and synchronizes hyperactivity induction with behavioral pattern alteration by suppressing viral virulence. Conserved amino acid residues were also identified in the coiled-coil domain of the Bm8 protein, which is required for suppressing viral virulence in cultured cells and larval hosts. Although bv/odv-e26 is previously thought to be conserved in a limited group of lepidopteran NPVs, our synteny-based bioinformatics approach discovered putative homologues in the genomes of most lepidopteran NPVs. Functional analyses revealed that phylogenetically close and distant bv/odv-e26 homologues possess suppressive activity with functionally essential common residues in their coiled-coil domains. Collectively, these findings indicate that baculovirus bv/odv-e26 is a conserved gene optimizing viral virulence for establishing behavioral manipulation in NPV-infected larval hosts. Author SummaryBaculovirus-induced host abnormal behavior has been described in various lepidopteran insects for a long time, although it is still largely unknown how the virus establishes this complex trait. We showed that baculovirus bv/odv-e26 is a factor that suppresses viral virulence and synchronizes hyperactivity and behavioral pattern alteration. We also revealed that putative bv/odv-e26 homologues are encoded by a wider range of baculoviruses than previously thought, with functionally conserved residues. We confirmed the suppressive function in both phylogenetically close and distant bv/odv-e26 homologues. These results indicate that acquiring a suppressive factor for viral virulence is a crucial event for the evolution of a host manipulation strategy by baculoviruses.