| First Author | Tachibana Y | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 6 | Pages | 112592 |
| PubMed ID | 37269286 | Mgi Jnum | J:338357 |
| Mgi Id | MGI:7511331 | Doi | 10.1016/j.celrep.2023.112592 |
| Citation | Tachibana Y, et al. (2023) Host genetics highlights IFN-gamma-dependent Toxoplasma genes encoding secreted and non-secreted virulence factors in in vivo CRISPR screens. Cell Rep 42(6):112592 |
| abstractText | Secreted virulence factors of Toxoplasma to survive in immune-competent hosts have been extensively explored by classical genetics and in vivo 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 in vivo 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-gamma (IFN-gamma)-dependent virulence genes. The screen results suggest a role of GRA72 for normal GRA17/GRA23 localization and the IFN-gamma-dependent role of UFMylation-related genes. Collectively, our study demonstrates that host genetics can complement in vivo CRISPR screens to highlight genes encoding IFN-gamma-dependent secreted and non-secreted virulence factors in Toxoplasma. |
