Strain-specific disruption of interferon-stimulated N-myc and STAT interactor (NMI) function by Toxoplasma gondii type I ROP18 in human cells. Issue 13 (30th November 2020)

• Record Type: Journal Article
• Authors: Xia, Jing; Blank, Matthew L.; Zhou, Li-Juan; Wu, Shui-Zhen; Peng, Hong-Juan; Boyle, Jon P.
• Is Part Of: Parasitology. Volume 147:Issue 13(2020)
• Page Start: 1433
• Page End: 1442
• Publication Date: 2020-11-30
• Subjects: Diversifying selection, -- NMI, -- ROP18, -- Toxoplasma gondii; Parasitology -- Periodicals; Electronic journals; 616.96
• DOI: 10.1017/S0031182020001249
• Languages: English
• ISSNs: 0031-1820

Abstract

Abstract: Toxoplasma gondii rhoptry protein Tg ROP18 is a polymorphic virulence effector that targets immunity-related GTPases (IRGs) in rodents. Given that IRGs are uniquely diversified in rodents and not in other T. gondii intermediate hosts, the role of Tg ROP18 in manipulating non-rodent cells is unclear. Here we show that in human cells Tg ROP18I interacts with the interferon-gamma-inducible protein N-myc and STAT interactor (NMI) and that this is a property that is unique to the type I Tg ROP18 allele. Specifically, when expressed ectopically in mammalian cells only Tg ROP18I co-immunoprecipitates with NMI in IFN-γ-treated cells, while Tg ROP18II does not. In parasites expressing Tg ROP18I or Tg ROP18II, NMI only co-immunoprecipitates with TgROP18I and this is associated with allele-specific immunolocalization of NMI on the parasitophorous vacuolar membrane (PVM). We also found that Tg ROP18I reduces NMI association with IFN-γ-activated sequences (GAS) in the IRF1 gene promoter. Finally, we determined that polymorphisms in the C-terminal kinase domain of Tg ROP18I are required for allele-specific effects on NMI. Together, these data further define new host pathway targeted by Tg ROP18I and provide the first function driven by allelic differences in the highly polymorphic ROP18 locus.