Translation initiation factor eIF1.2 promotesToxoplasmastage conversion by regulating levels of key differentiation factors

Abstract

AbstractsThe parasiteToxoplasma gondiipersists in its hosts by converting from replicating tachyzoites to latent bradyzoites housed in tissue cysts. The molecular mechanisms that mediateT. gondiidifferentiation remain poorly understood. Through a mutagenesis screen, we identified translation initiation factor eIF1.2 as a critical factor forT. gondiidifferentiation. A F97L mutation in eIF1.2 or the genetic ablation of eIF1.2 (ΔeIF1.2) markedly impeded bradyzoite cyst formationin vitroandin vivo. We demonstrated, at single-molecule level, that the eIF1.2 F97L mutation impacts the scanning process of the ribosome preinitiation complex on a model mRNA. RNA sequencing and ribosome profiling experiments unveiled that ΔeIF1.2parasites are defective in the upregulating bradyzoite induction factors BFD1 and BFD2 during stress-induced differentiation. Forced expression of BFD1 or BFD2 significantly restored differentiation in ΔeIF1.2parasites. Together, our findings suggest that eIF1.2 functions by regulating the translation of key differentiation factors necessary to establish chronic toxoplasmosis.