ArticleProceedings of the National Academy of Sciences of the United States of America2011
Virulence differences in Toxoplasma mediated by amplification of a family of polymorphic pseudokinases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 1 of them a synthesis that pooled it.
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Who cites it
138 citing papers in PubMed, 1 synthesis or guideline pooled it, 224 citations in OpenAlex.
- Is Toxoplasma gondii type related to clinical outcome in human congenital infection? Systematic and critical review.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2016Pooled it
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- Characterization of ovine abortion in Uruguay reveals extensive non-clonal diversity and multiple evolutionary origins of Toxoplasma gondii.Scientific reports · 2026Article
- Cysteine-S-nitrosylation inhibits Rop5-mediated immune evasion inbioRxiv : the preprint server for biology · 2025Article
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- Multiple Typing Approach to CharacterizeAnimals : an open access journal from MDPI · 2024Article
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- Proteomic approaches for protein kinase substrate identification in Apicomplexa.Molecular and biochemical parasitology · 2024Review
- CRISPR-based functional profiling of the Toxoplasma gondii genome during acute murine infection.Nature microbiology · 2024Article
- Effective factors in the pathogenesis ofHeliyon · 2024Review
- The role of IFN-γ-mediated host immune responses in monitoring and the elimination of Toxoplasma gondii infection.International immunology · 2024Review
- Susceptibility ofmBio · 2024Article
- Structural basis of Irgb6 inactivation by Toxoplasma gondii through the phosphorylation of switch I.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
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- IFNs in host defence and parasite immune evasion duringFrontiers in immunology · 2024Review
- A Combination of Four Nuclear Targeted Effectors ProtectsbioRxiv : the preprint server for biology · 2023Article
- Genetic diversity of Toxoplasma gondii in South America: occurrence, immunity, and fate of infection.Parasites & vectors · 2023Review
- Article
- A ring trial to harmonize Toxoplasma gondii microsatellite typing: comparative analysis of results and recommendations for optimization.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2023Article
- A heterotrimeric complex of Toxoplasma proteins promotes parasite survival in interferon gamma-stimulated human cells.PLoS biology · 2023Article
78 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The population structure of Toxoplasma gondii includes three highly prevalent clonal lineages referred to as types I, II, and III, which differ greatly in virulence in the mouse model. Previous studies have implicated a family of serine/threonine protein kinases found in rhoptries (ROPs) as important in mediating virulence differences between strain types. Here, we explored the genetic basis of differences in virulence between the highly virulent type I lineage and moderately virulent type II based on successful genetic cross between these lineages. Genome-wide association revealed that a single quantitative trait locus controls the dramatic difference in lethality between these strain types. Neither ROP16 nor ROP18, previously implicated in virulence of T. gondii, was found to contribute to differences between types I and II. Instead, the major virulence locus contained a tandem cluster of polymorphic alleles of ROP5, which showed similar protein expression between strains. ROP5 contains a conserved serine/threonine protein kinase domain that includes only part of the catalytic triad, and hence, all members are considered to be pseudokinases. Genetic disruption of the entire ROP5 locus in the type I lineage led to complete attenuation of acute virulence, and complementation with ROP5 restored lethality to WT levels. These findings reveal that a locus of polymorphic pseudokinases plays an important role in pathogenesis of toxoplasmosis in the mouse model.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.