Polydnaviral Ankyrin Proteins Aid Parasitic Wasp Survival by Coordinate and Selective Inhibition of Hematopoietic and Immune NF-kappa B Signaling in Insect Hosts

Abstract

Polydnaviruses are mutualists of their parasitoid wasps and express genes in immune cells of their Lepidopteran hosts. Polydnaviral genomes carry multiple copies of viral ankyrins or vankyrins. Vankyrin proteins are homologous to IκB proteins, but lack sequences for regulated degradation. We tested if Ichnoviral Vankyrins differentially impede Toll-NF-κB-dependent hematopoietic and immune signaling in a heterologous in vivo Drosophila, system. We first show that hematopoiesis and the cellular encapsulation response against parasitoid wasps are tightly-linked via NF-κB signaling. The niche, which neighbors the larval hematopoietic progenitors, responds to parasite infection. Drosophila NF-κB proteins are expressed in the niche, and non cell-autonomously influence fate choice in basal and parasite-activated hematopoiesis. These effects are blocked by the Vankyrin I ²-vank-3, but not by P-vank-1, as is the expression of a NF-κB target transgene. I ²-vank-3 and P-vank-1 differentially obstruct cellular and humoral inflammation. Additionally, their maternal expression weakens ventral embryonic patterning. We propose that selective perturbation of NF-κB-IκB interactions in natural hosts of parasitic wasps negatively impacts the outcome of hematopoietic and immune signaling and this immune deficit contributes to parasite survival and species success in nature.

Author Summary

Parasitoid wasps are insects whose development takes place within the body of other insects. To survive, wasp larvae must overcome the immune defenses of their hosts. How parasitic wasps overcome host immunity is not fully understood even though we know that different strategies using venoms, virus-like particles, or viruses are involved. A unique class of viruses, called polydnaviruses is found in two families of wasps that comprise more than 20,000 wasp species. The genomes of polydnaviruses encode proteins with ankyrin repeats. Ankyrin repeats are also found in Cactus, the inhibitor protein of NF-κB signaling in Drosophila. Viral ankyrin proteins, or Vankyrins, however, lack the amino acid sequences necessary for turnover found in Cactus and mammalian IκB family members. We show that Vankyrins produced by polydnaviruses of a parasitic wasp that attacks caterpillars of many common agricultural pests can block NF-κB signaling in fruit fly larvae. This inhibition supports parasite success. Our work highlights the crucial role of NF-κB signaling across insect taxa in insect-insect and insect-virus interactions. Studies of polydnaviral ankyrin proteins in Drosophila reveal that immune-suppressive viruses may block both cellular and humoral immunity in insects to win the biological ‘arms race’.