Over-expression Screen of Interferon-Stimulated Genes Identifies RARRES3 as a Restrictor ofToxoplasma gondiiInfection

Toxoplasma gondiiis an important human pathogen infecting an estimated 1 in 3 people worldwide. The cytokine interferon gamma (IFNγ) is induced during infection and is critical for restrictingT. gondiigrowth in human cells. Growth restriction is presumed to be due to the induction interferon stimulated genes (ISGs) that are upregulated to protect the host from infection. Although there are hundreds of ISGs induced by IFNγ, their individual roles in restricting parasite growth in human cells remain somewhat elusive. To address this deficiency, we screened a library of 414 IFNγ induced ISGs to identify factors that impactT. gondiiinfection in human cells. In addition to IRF1, which likely acts through induction of numerous downstream genes, we identified RARRES3 as a single factor that restrictsT. gondiiinfection by inducing premature egress of the parasite in multiple human cell lines. Overall, while we successfully identified a novel IFNγ induced factor restrictingT. gondiiinfection, the limited number of ISGs capable of restrictingT. gondiiinfection when individually expressed suggests that IFNγ mediated immunity toT. gondiiinfection is a complex, multifactorial process.