Abstract
Secreted virulence factors of Toxoplasma to survive in immune-competent hosts have been extensively explored by classical genetics and invivo CRISPR screen methods, whereas their requirements in immune-deficient hosts are incompletely understood. Those of non-secreted virulence factors are further enigmatic. Here we develop an invivo CRISPR screen system to enrich not only secreted but also non-secreted virulence factors in virulent Toxoplasma-infected C57BL/6 mice. Notably, combined usage of immune-deficient Ifngr1-/- mice highlights genes encoding various non-secreted proteins as well as well-known effectors such as ROP5, ROP18, GRA12, and GRA45 as interferon-γ (IFN-γ)-dependent virulence genes. The screen results suggest a role of GRA72 for normal GRA17/GRA23 localization and the IFN-γ-dependent role of UFMylation-related genes. Collectively, our study demonstrates that host genetics can complement invivo CRISPR screens to highlight genes encoding IFN-γ-dependent secreted and non-secreted virulence factors in Toxoplasma.
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