Affinage · Toxoplasma gondii

GRA6

dense granule protein GRA6 · UniProt A0A125YS55

Annotated
2026-09-08
99 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRA6 is a dense granule protein of Toxoplasma gondii that is secreted into the parasitophorous vacuole (PV), where it functions both as a structural organizer of the intravacuolar network (IVN) and as a strain-polymorphic effector of host signaling and antigen presentation (PMID:7637717, PMID:25225460, PMID:26628378). After secretion from the anterior pole, GRA6 is translocated to the posterior end of the parasite and associates with the nascent IVN membranes predominantly through hydrophobic interactions, forming a stable multimeric complex with GRA2 and GRA4 (PMID:10498186). Its correct posterior localization depends on GRA2, and GRA6 is in turn required for the mature nanotubular conformation of the IVN, since Δgra6 vacuoles accumulate small vesicles rather than elongated tubules (PMID:12134078); in a reconstituted cell-free system GRA6 and GRA2 are sufficient to shape membrane tubules (PMID:26628378). This GRA2/GRA6-stabilized network contributes to sequestration of host Rab11A vesicles within the PV (PMID:29070609) and promotes brain tissue cyst development during chronic type II infection (PMID:21531875). GRA6 also acts as a host-manipulating effector, selectively activating the transcription factor NFAT4 through CAMLG in a manner dependent on a C-terminal polymorphism that makes type I strains far more potent than type II, driving myeloid cell recruitment and chemokine induction (PMID:25225460). Independently, GRA6 supplies the immunodominant, ERAAP-dependent decapeptide HF10 presented by H-2Ld to protective CD8+ T cells, with immunodominance dictated by the C-terminal position of the epitope (PMID:18587399, PMID:23818852), and epitope accessibility governed by GRA6 membrane topology—PV-membrane insertion favors presentation whereas IVN association limits it (PMID:26628378).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 High

    Establishing that GRA6 is a dense granule antigen that relocates to the intravacuolar network defined it as a secreted structural component of the PV rather than a purely cytosolic parasite protein.

    Evidence cDNA cloning/sequencing plus immunofluorescence and immunoelectron microscopy localization

    PMID:7637717

    Open questions at the time
    • Function of the two hydrophobic domains and glycine-rich C-terminus not tested
    • No interacting partners identified
  2. 1996 Medium

    Mapping cis-acting promoter elements answered how GRA6 expression is transcriptionally controlled, identifying repeated A/TGAGACG motifs shared with other GRA genes.

    Evidence CAT reporter deletion and mutation analysis in transient transformation

    PMID:8858595

    Open questions at the time
    • Trans-acting factors binding these motifs not identified
    • Regulation across life stages not addressed
  3. 1997 Medium

    Comparing life stages revealed that GRA6 secretion behavior is stage-specific, being retained in cytoplasmic granules during sporozoite invasion rather than secreted into the vacuole.

    Evidence Immunofluorescence and immunoblot comparing sporozoite versus tachyzoite behavior

    PMID:9353039

    Open questions at the time
    • Molecular basis of stage-specific retention unknown
    • Consequence for sporozoite PV biology untested
  4. 1999 High

    Biochemical dissection of GRA6 membrane association showed it binds IVN membranes via hydrophobic interactions and forms a defined complex with GRA2 and GRA4, moving from localization to a molecular assembly model.

    Evidence Cell fractionation, denaturing treatment, cross-linking, and electron microscopy

    PMID:10498186

    Open questions at the time
    • Stoichiometry and interface of the GRA2/GRA4/GRA6 complex not resolved
    • Role of GRA6 phosphorylation not functionally defined
  5. 2000 Medium

    Sequencing GRA6 across strains established a genotype-phenotype correlation, linking GRA6 polymorphisms to strain lineage and murine virulence and providing a genotyping tool.

    Evidence PCR/sequencing of GRA6 across 30 strains and PCR-RFLP with MseI

    PMID:10779578

    Open questions at the time
    • Correlation is not a demonstrated causal mechanism
    • Functional consequence of specific polymorphisms not tested here
  6. 2000 Medium

    Domain mapping of the human antibody response identified the N-terminal hydrophilic region as the immunodominant B-cell region of GRA6, informing serodiagnostic use.

    Evidence Reactivity of recombinant N- versus C-terminal domains with human sera by immunoblot and ELISA

    PMID:10882660

    Open questions at the time
    • Does not address T-cell epitope location
    • Single serum panel
  7. 2002 High

    Knockout epistasis established that GRA6 is required for the mature nanotubular architecture of the IVN and that its posterior localization is GRA2-dependent, defining a hierarchy within the network-building machinery.

    Evidence Δgra6 and Δgra2 knockouts, EM/IF ultrastructural analysis, complementation with mutant GRA2

    PMID:12134078

    Open questions at the time
    • Mechanism by which GRA6 remodels vesicles into tubules not resolved at this stage
    • Consequence of altered IVN for parasite fitness not measured
  8. 2008 High

    Identifying GRA6 as the source of the ERAAP-processed HF10/H-2Ld epitope explained a major immunodominant CD8+ T cell response and linked antigen processing machinery to protective immunity.

    Evidence Epitope identification, T cell assays, and ERAAP-knockout mouse infection

    PMID:18587399

    Open questions at the time
    • Why GRA6-derived HF10 is preferentially processed not yet explained
    • Restricted to BALB/c H-2Ld context
  9. 2008 Medium

    Characterization of GRA12 showed it co-purifies with GRA2 and shares GRA6's trafficking route, extending the composition of the GRA2-anchored IVN complex that includes GRA6.

    Evidence IF/immunoEM, GRA2-knockout analysis, and affinity chromatography with tagged GRA2

    PMID:18840447

    Open questions at the time
    • Direct GRA6-GRA12 interaction not demonstrated
    • GRA6 is a comparator rather than the primary subject
  10. 2011 High

    Deletion and complementation in type II parasites established that GRA6 promotes brain cyst development, linking an IVN structural protein to chronic latent infection.

    Evidence Δgra6 in type II Δku80, mouse brain cyst counting, and complementation at the UPRT locus

    PMID:21531875

    Open questions at the time
    • Whether the cyst defect reflects IVN disruption or another GRA6 activity is unresolved
    • Molecular pathway to cyst formation not defined
  11. 2013 High

    Epitope-repositioning experiments showed that GRA6 immunodominance is dictated by the C-terminal position of HF10, not by MHC affinity or precursor frequency, defining a positional rule for antigen presentation and protection.

    Evidence Epitope-repositioned GRA6 variant parasites, in vivo CD8 T cell responses, and parasite burden measurement

    PMID:23818852

    Open questions at the time
    • Mechanistic basis of the C-terminal positional advantage not fully defined
    • Generality to other GRA epitopes untested
  12. 2014 High

    Discovery that GRA6 selectively activates NFAT4 via CAMLG in a strain-polymorphism-dependent manner recast GRA6 as a host-signaling effector controlling immune cell recruitment and virulence.

    Evidence GRA6 overexpression and knockout, NFAT4-knockout mice, chemokine analysis, and NFAT inhibitor treatment

    PMID:25225460

    Open questions at the time
    • How PV-resident GRA6 engages host CAMLG topologically not resolved
    • Precise polymorphic residues driving type I vs type II potency not enumerated here
  13. 2015 High

    Cell-free reconstitution and presentation assays unified GRA6 structural and immunological roles, showing GRA6/GRA2 shape membrane tubules and that GRA6 membrane topology (PV membrane insertion vs IVN association) gates its MHC I accessibility.

    Evidence Cell-free minimal membrane system, MHC I presentation assays, in vivo CD8 T cell responses, GRA6/GRA2 knockouts

    PMID:26628378

    Open questions at the time
    • What controls partitioning of GRA6 between PV membrane and IVN in vivo is unresolved
    • Link between topology and NFAT4 signaling not directly tested
  14. 2017 Medium

    Double-knockout imaging tied the GRA2/GRA6-stabilized IVN to host vesicle sequestration, connecting network architecture to nutrient/host-vesicle acquisition.

    Evidence Δgra2 and Δgra2Δgra6 parasites, correlative light-electron microscopy, and live GFP-Rab11A imaging

    PMID:29070609

    Open questions at the time
    • Δgra6 single-knockout effect on Rab11A not tested alone
    • Functional consequence of Rab11A sequestration for the parasite not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GRA6 is partitioned between the PV membrane and the IVN in vivo, and how this topology mechanistically couples its structural, host-signaling (NFAT4/CAMLG), and antigen-presentation functions, remains unresolved.
  • Regulators of GRA6 membrane topology unknown
  • Structural interface of the GRA2/GRA4/GRA6 complex undetermined
  • Direct GRA6-CAMLG interaction and its topological requirement not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
CAMLG (HOST)ERAAP (HOST ANTIGEN-PROCESSING AMINOPEPTIDASE)GRA12 (CO-COMPLEX VIA GRA2)GRA2GRA4NFAT4 (HOST, ACTIVATED DOWNSTREAM)
Complex memberships
GRA2-GRA4-GRA6 multimeric intravacuolar network complexGRA2-associated IVN complex including GRA12

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 GRA6 is a 32 kDa dense granule antigen that is localized to the dense granules of tachyzoites and, following secretion, associates with the intravacuolar network of the parasitophorous vacuole. The gene encodes a 230-amino-acid polypeptide with two hydrophobic transmembrane-like domains; the N-terminal domain lacks classical signal peptide features, and the C-terminal hydrophilic region is glycine-rich (24%), suggesting a structural role in the network. cDNA cloning, gene sequencing, immunolocalization with specific antiserum (immunofluorescence and immunoelectron microscopy), primer extension analysis Molecular and biochemical parasitology High 7637717
1999 Following secretion into the parasitophorous vacuole, GRA6 is rapidly translocated to the posterior end of the parasite where it binds to a cluster of multi-lamellar vesicles that give rise to the intravacuolar network. GRA6 association with network membranes is predominantly mediated by hydrophobic interactions, and a phosphorylated form of GRA6 shows increased membrane association. Cross-linking studies established that GRA4 and GRA6 specifically interact with GRA2 to form a multimeric complex stably associated with the intravacuolar network. Cell fractionation, denaturing agent treatment, cross-linking studies, immunofluorescence microscopy, immunoelectron microscopy Molecular and biochemical parasitology High 10498186
2002 GRA6 is required for the normal nanotubular conformation of the intravacuolar network (IVN). Deletion of GRA6 (Δgra6 mutant) leads to an altered mature network characterized by small vesicles instead of elongated nanotubules; however, the initial formation of the posterior organizing center was normal in Δgra6 parasites (in contrast to Δgra2 parasites). GRA6 also failed to localize properly to the posterior organizing center in Δgra2 cells, indicating GRA2-dependent localization of GRA6. Gene knockout (Δgra6 and Δgra2 mutants), immunofluorescence microscopy, electron microscopy, complementation with mutated GRA2 forms Molecular biology of the cell High 12134078
2008 GRA6 is the source of the immunodominant and protective decapeptide HF10 presented by the H-2L(d) MHC class I molecule in BALB/c mice. Presentation of the HF10-H-2L(d) ligand required proteolysis by ERAAP (the endoplasmic reticulum aminopeptidase associated with antigen processing), and expansion of protective CD8+ T cell populations was impaired in ERAAP-deficient mice infected with T. gondii. Peptide identification from infected cells, T cell assays, ERAAP knockout mouse infection, CD8+ T cell expansion assays Nature immunology High 18587399
2011 GRA6 (together with GRA4) plays a functional role in brain cyst development and latent infection in type II T. gondii. Deletion of GRA6 in type II Δku80 parasites drastically reduced brain tissue cyst burdens in mice. Complementation with a functional GRA6 allele at the endogenous UPRT locus significantly restored cyst burdens, confirming the specific role of GRA6. Gene knockout in type II Δku80 background, mouse infection model with brain cyst counting, genetic complementation Eukaryotic cell High 21531875
2013 The location of the GRA6 peptide epitope at the C-terminus of the GRA6 antigenic precursor determines immunodominance and optimal MHC I processing. Parasite burden is controlled by GRA6-specific CD8 T cells but not by responses to subdominant GRA4- and ROP7-derived epitopes. Optimal processing and immunodominance were determined by the C-terminal position of the epitope, not by peptide affinity for MHC I or precursor T cell frequency. Genetically modified parasites expressing epitope-repositioned GRA6 variants, in vivo CD8 T cell response assays, parasite burden measurements PLoS pathogens High 23818852
2014 The polymorphic dense granule protein GRA6 selectively activates the host transcription factor NFAT4 via CAMLG. GRA6 overexpression robustly and selectively activated NFAT4. Infection with wild-type but not GRA6-deficient parasites induced NFAT4 activation. GRA6-deficient parasites exhibited reduced virulence in local infection. NFAT4-deficient mice showed prolonged survival, decreased CD11b+Ly6G+ cell recruitment, and impaired expression of chemokines Cxcl2 and Ccl2. Type I parasites caused significantly higher NFAT4 activation than type II parasites due to a polymorphism in the C-terminus of GRA6. GRA6 overexpression, GRA6 gene knockout, NFAT4 knockout mice, in vivo infection assays, flow cytometry, chemokine expression analysis, NFAT inhibitor treatment The Journal of experimental medicine High 25225460
2015 GRA6 membrane association in the parasitophorous vacuole regulates its accessibility to the MHC class I antigen presentation pathway. Using a cell-free minimal system, GRA6 and GRA2 were shown to shape membrane tubules. Insertion of GRA6 in the PV membrane is key for immunogenicity, whereas association of GRA6 with the IVN limits MHC I presentation and curtails GRA6-specific CD8 T cell responses in mice. Cell-free minimal membrane system reconstitution, MHC I presentation assays in infected cells, CD8 T cell response quantification in mice, GRA6/GRA2 knockout parasites Cell reports High 26628378
2017 GRA6 (together with GRA2) contributes to host vesicle sequestration within the parasitophorous vacuole. Rab11A vesicles concentrate at the intravacuolar network (IVN), but this concentration is reduced in Δgra2 and Δgra2Δgra6 parasites, suggesting that IVN tubules stabilized by GRA2 and GRA6 contribute to host vesicle sequestration. Genetic knockout (Δgra2, Δgra2Δgra6), correlative light and electron microscopy, live imaging of GFP-Rab11A vesicles The Journal of cell biology Medium 29070609
1996 The promoter of GRA6 contains cis-acting elements critical for expression. Deletion analysis mapped optimal GRA6 promoter activity to a region -146 to -27 bp upstream of the transcription start site. Repeated motifs (A/TGAGACG) found in either orientation within these proximal regions are critical elements for promoter activity of GRA6 (and other GRA genes). Transient transformation with CAT reporter gene constructs, deletion analysis of promoter regions, mutation analysis of cis-elements Molecular microbiology Medium 8858595
2000 GRA6 sequence polymorphisms correlate with T. gondii strain type and murine virulence. Sequence alignment of the GRA6 coding region (690 bp) across 30 strains from 8 zymodemes identified 24 polymorphic nucleotide positions distinguishing types I, II, and III. Type II strains have unique deletions of 15 bp and 3 bp causing loss of 6 amino acids. A PCR-RFLP method using MseI was developed to distinguish the three lineages based on GRA6 polymorphisms. PCR amplification and DNA sequencing of GRA6 coding region from 30 strains, sequence alignment, PCR-RFLP with MseI enzyme International journal for parasitology Medium 10779578
1997 In sporozoites, GRA6 protein is present in dense granules and is detected in oocyst extracts, but unlike tachyzoite behavior, GRA6 (along with GRA1, GRA2, GRA4) is retained within cytoplasmic granules during sporozoite invasion of host cells and is not secreted into the first parasitophorous vacuole (PV1). This establishes a stage-specific difference in GRA6 secretion behavior. Immunofluorescence with anti-GRA antibodies on sporozoite-infected cells, comparison of tachyzoite vs sporozoite secretion, oocyst extract immunoblot Infection and immunity Medium 9353039
2000 The N-terminal hydrophilic region of GRA6 (but not the C-terminal region) is recognized by human anti-Toxoplasma sera. Recombinant GST-GRA6-Nt ELISA achieved 96% sensitivity for detection of T. gondii IgG in human sera, demonstrating that the N-terminal hydrophilic domain is the immunodominant region of GRA6 in humans. Recombinant protein expression in E. coli (separate N- and C-terminal domains), immunoblot with pooled human sera, ELISA with 100 positive and 98 negative human sera Clinical and diagnostic laboratory immunology Medium 10882660
2008 GRA12 behaves similarly to GRA6 in that it is secreted into the PV from the anterior pole, transits to the posterior invagination where the IVN assembles, and finally resides in the vacuolar space associated with the mature nanotubular network. GRA12 fails to localize at the parasite posterior end in the absence of GRA2, similar to GRA6. Affinity chromatography using tagged GRA2 co-purified GRA12 with GRA2 in both parasite and PV soluble fractions, placing GRA12 in the same GRA protein complex that includes GRA6. Immunofluorescence, immunoelectron microscopy, GRA2 knockout analysis, affinity chromatography with tagged GRA2 International journal for parasitology Medium 18840447

Source papers

Stage 0 corpus · 99 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Population structure and mouse-virulence of Toxoplasma gondii in Brazil. International journal for parasitology 278 17963770
2011 Genetic analyses of atypical Toxoplasma gondii strains reveal a fourth clonal lineage in North America. International journal for parasitology 232 21320505
2008 Immunodominant, protective response to the parasite Toxoplasma gondii requires antigen processing in the endoplasmic reticulum. Nature immunology 175 18587399
2010 Direct detection and genotyping of Toxoplasma gondii in meat samples using magnetic capture and PCR. International journal of food microbiology 157 20350771
2011 Type II Toxoplasma gondii KU80 knockout strains enable functional analysis of genes required for cyst development and latent infection. Eukaryotic cell 153 21531875
2008 Type X Toxoplasma gondii in a wild mussel and terrestrial carnivores from coastal California: new linkages between terrestrial mammals, runoff and toxoplasmosis of sea otters. International journal for parasitology 153 18452923
2007 High prevalence and abundant atypical genotypes of Toxoplasma gondii isolated from lambs destined for human consumption in the USA. International journal for parasitology 148 18191859
2002 Biogenesis of nanotubular network in Toxoplasma parasitophorous vacuole induced by parasite proteins. Molecular biology of the cell 141 12134078
2004 An unusual genotype of Toxoplasma gondii is common in California sea otters (Enhydra lutris nereis) and is a cause of mortality. International journal for parasitology 135 15003489
2011 Genetic characterisation of Toxoplasma gondii in wildlife from North America revealed widespread and high prevalence of the fourth clonal type. International journal for parasitology 131 21802422
2006 Biologic and genetic comparison of Toxoplasma gondii isolates in free-range chickens from the northern Pará state and the southern state Rio Grande do Sul, Brazil revealed highly diverse and distinct parasite populations. Veterinary parasitology 126 16982151
2000 Molecular typing of Toxoplasma gondii strains by GRA6 gene sequence analysis. International journal for parasitology 122 10779578
2007 Genetic and biologic characterization of Toxoplasma gondii isolates of cats from China. Veterinary parasitology 117 17267132
2013 Genetic characterization of Toxoplasma gondii revealed highly diverse genotypes for isolates from newborns with congenital toxoplasmosis in southeastern Brazil. Journal of clinical microbiology 116 23284022
2013 Genotypes and mouse virulence of Toxoplasma gondii isolates from animals and humans in China. PloS one 107 23308233
2009 Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring. Microbes and infection 107 19638313
2003 Serotyping of Toxoplasma gondii infections in humans using synthetic peptides. The Journal of infectious diseases 106 12717631
2009 Genetic characterization of Toxoplasma gondii isolates from China. Parasitology international 104 19567233
2011 High prevalence and genotypes of Toxoplasma gondii isolated from goats, from a retail meat store, destined for human consumption in the USA. International journal for parasitology 96 21515278
2008 Genetic diversity of Toxoplasma gondii isolates from chickens from Brazil. Veterinary parasitology 95 18804329
2014 Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA6. The Journal of experimental medicine 93 25225460
2007 Occurrence of Toxoplasma gondii and Hammondia hammondi oocysts in the faeces of cats from Germany and other European countries. Veterinary parasitology 93 18226453
1999 Differential membrane targeting of the secretory proteins GRA4 and GRA6 within the parasitophorous vacuole formed by Toxoplasma gondii. Molecular and biochemical parasitology 93 10498186
2006 Serotyping of Toxoplasma gondii in chronically infected pregnant women: predominance of type II in Europe and types I and III in Colombia (South America). Microbes and infection 92 16938480
2011 Molecular genotyping of Toxoplasma gondii from Central and South America revealed high diversity within and between populations. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 91 22226702
2010 Prevalence and genotypes of Toxoplasma gondii in feline faeces (oocysts) and meat from sheep, cattle and pigs in Switzerland. Veterinary parasitology 87 21183278
1995 Characterization of a dense granule antigen of Toxoplasma gondii (GRA6) associated to the network of the parasitophorous vacuole. Molecular and biochemical parasitology 79 7637717
2011 Genotyping of Toxoplasma gondii isolates from cats in different geographic regions of China. Veterinary parasitology 78 21757292
2007 Prevalence of Toxoplasma gondii in dogs from Colombia, South America and genetic characterization of T. gondii isolates. Veterinary parasitology 77 17257761
2011 Toxoplasma gondii isolates: multilocus RFLP-PCR genotyping from human patients in Sao Paulo State, Brazil identified distinct genotypes. Experimental parasitology 76 21741380
2009 Atypical Toxoplasma gondii genotypes identified in oocysts shed by cats in Germany. International journal for parasitology 76 19695254
2007 Isolation and molecular characterization of Toxoplasma gondii strains from different hosts in Iran. Parasitology research 74 17333278
2017 The parasite Toxoplasma sequesters diverse Rab host vesicles within an intravacuolar network. The Journal of cell biology 73 29070609
2013 Toxoplasma gondii prevalence in food animals and rodents in different regions of China: isolation, genotyping and mouse pathogenicity. Parasites & vectors 72 24330536
2000 Identification and molecular characterization of GRA8, a novel, proline-rich, dense granule protein of Toxoplasma gondii. Molecular and biochemical parasitology 70 10613696
2006 Characterization of Toxoplasma gondii isolates in free-range chickens from Chile, South America. Veterinary parasitology 68 16672177
2010 Genetic characterization of Toxoplasma gondii isolates from pigs in China. The Journal of parasitology 67 20481661
2007 Evaluation of protective effect of recombinant dense granule antigens GRA2 and GRA6 formulated in monophosphoryl lipid A (MPL) adjuvant against Toxoplasma chronic infection in mice. Vaccine 67 17418457
2009 Population biology of Toxoplasma gondii: what's out and where did they come from. Memorias do Instituto Oswaldo Cruz 62 19430643
2008 Seroprevalence and isolation of Toxoplasma gondii from free-range chickens in Ghana, Indonesia, Italy, Poland, and Vietnam. The Journal of parasitology 62 18372623
2007 Prevalence of Toxoplasma gondii in dogs from Sri Lanka and genetic characterization of the parasite isolates. Veterinary parasitology 62 17442491
2007 Diverse and atypical genotypes identified in Toxoplasma gondii from dogs in São Paulo, Brazil. The Journal of parasitology 61 17436942
2008 Genotyping studies of Toxoplasma gondii isolates from Africa revealed that the archetypal clonal lineages predominate as in North America and Europe. Veterinary parasitology 60 18583059
2014 Overlapping Toxoplasma gondii genotypes circulating in domestic animals and humans in Southeastern Brazil. PloS one 59 24587295
2006 Prevalence of Toxoplasma gondii in cats from Colombia, South America and genetic characterization of T. gondii isolates. Veterinary parasitology 59 16797845
2012 High prevalence and genotypes of Toxoplasma gondii isolated from organic pigs in northern USA. Veterinary parasitology 58 22483557
2014 Genetic characterization of Toxoplasma gondii from Brazilian wildlife revealed abundant new genotypes. International journal for parasitology. Parasites and wildlife 57 25426424
2010 Evaluation of immune responses in sheep induced by DNA immunization with genes encoding GRA1, GRA4, GRA6 and GRA7 antigens of Toxoplasma gondii. Veterinary parasitology 57 21251760
2009 Isolation of Toxoplasma gondii from animals in Durango, Mexico. The Journal of parasitology 57 18925790
2015 Seroprevalence and genetic characterization of Toxoplasma gondii in cancer patients in Anhui Province, Eastern China. Parasites & vectors 56 25889184
2012 The Toxoplasma gondii peptide AS15 elicits CD4 T cells that can control parasite burden. Infection and immunity 54 22778097
2007 Isolation and genotyping of Toxoplasma gondii from Ugandan chickens reveals frequent multiple infections. Parasitology 53 17892617
2007 High prevalence of unusual genotypes of Toxoplasma gondii infection in pork meat samples from Erechim, Southern Brazil. Anais da Academia Brasileira de Ciencias 53 17401480
2008 Serotyping of Toxoplasma gondii: striking homogeneous pattern between symptomatic and asymptomatic infections within Europe and South America. Microbes and infection 52 18539501
2015 Intravacuolar Membranes Regulate CD8 T Cell Recognition of Membrane-Bound Toxoplasma gondii Protective Antigen. Cell reports 51 26628378
2013 Genetic characterization of Toxoplasma gondii from pigs from different localities in China by PCR-RFLP. Parasites & vectors 51 23919620
2013 Location of the CD8 T cell epitope within the antigenic precursor determines immunogenicity and protection against the Toxoplasma gondii parasite. PLoS pathogens 51 23818852
1997 Toxoplasma gondii sporozoites form a transient parasitophorous vacuole that is impermeable and contains only a subset of dense-granule proteins. Infection and immunity 51 9353039
2012 Isolation and characterization of Toxoplasma gondii strains from stray cats revealed a single genotype in Beijing, China. Veterinary parasitology 50 22326429
2010 Isolation and genetic characterisation of Toxoplasma gondii from a red-handed howler monkey (Alouatta belzebul), a jaguarundi (Puma yagouaroundi), and a black-eared opossum (Didelphis aurita) from Brazil. Veterinary parasitology 50 21055880
2008 GRA12, a Toxoplasma dense granule protein associated with the intravacuolar membranous nanotubular network. International journal for parasitology 50 18840447
2014 Genetic characterization of Toxoplasma gondii from cats in Yunnan Province, Southwestern China. Parasites & vectors 49 24725959
2007 Transplacental toxoplasmosis in naturally-infected white-tailed deer: Isolation and genetic characterisation of Toxoplasma gondii from foetuses of different gestational ages. International journal for parasitology 49 18187136
2014 Using molecular epidemiology to track Toxoplasma gondii from terrestrial carnivores to marine hosts: implications for public health and conservation. PLoS neglected tropical diseases 48 24874796
2010 Direct genotypic characterization of Toxoplasma gondii strains associated with congenital toxoplasmosis in Tunisia (North Africa). The American journal of tropical medicine and hygiene 48 20519598
2009 Genetic diversity among capybara (Hydrochaeris hydrochaeris) isolates of Toxoplasma gondii from Brazil. Veterinary parasitology 48 19375864
2007 Genetic characterization of Toxoplasma gondii isolates in dogs from Vietnam suggests their South American origin. Veterinary parasitology 48 17442492
2011 DNA vaccination with a gene encoding Toxoplasma gondii GRA6 induces partial protection against toxoplasmosis in BALB/c mice. Parasites & vectors 47 22070984
2000 Enzyme-linked immunosorbent assays using the recombinant dense granule antigens GRA6 and GRA1 of Toxoplasma gondii for detection of immunoglobulin G antibodies. Clinical and diagnostic laboratory immunology 47 10882660
2018 Bioinformatics analysis of single and multi-hybrid epitopes of GRA-1, GRA-4, GRA-6 and GRA-7 proteins to improve DNA vaccine design against Toxoplasma gondii. Journal of parasitic diseases : official organ of the Indian Society for Parasitology 46 29844632
2012 Prevalence and genotypes of Toxoplasma gondii in pork from retail meat stores in Eastern China. International journal of food microbiology 46 22781578
2012 First report of genotyping of Toxoplasma gondii isolates from wild birds in China. The Journal of parasitology 46 22263675
2011 Toxoplasma gondii in foxes and rodents from the German Federal States of Brandenburg and Saxony-Anhalt: seroprevalence and genotypes. Veterinary parasitology 46 22105083
2010 Analysis of marine bivalve shellfish from the fish market in Santos city, São Paulo state, Brazil, for Toxoplasma gondii. Veterinary parasitology 46 20197214
1996 Common cis-acting elements critical for the expression of several genes of Toxoplasma gondii. Molecular microbiology 46 8858595
2007 Genetic diversity among sea otter isolates of Toxoplasma gondii. Veterinary parasitology 45 18155841
2007 Toxoplasma gondii: genotyping of strains from Brazilian AIDS patients with cerebral toxoplasmosis by multilocus PCR-RFLP markers. Experimental parasitology 45 17950282
2010 Genetic diversity of Toxoplasma gondii isolates in Egyptian feral cats reveals new genotypes. The Journal of parasitology 44 21158618
2006 Toxoplasma gondii: an evaluation of diagnostic value of recombinant antigens in a murine model. Experimental parasitology 44 16707125
2025 Human Retinal Organoid Model of Ocular Toxoplasmosis. Pathogens (Basel, Switzerland) 5 40137771
2025 Detection of Toxoplasma gondii (Types I, II, III and 12) and Sarcocystis spp. in the brains of river otter (Lontra canadensis) from Alberta, Canada. International journal for parasitology. Parasites and wildlife 3 40276325
2025 New genetic variants of Toxoplasma gondii isolates and a novel ROP5 allele in free-range chickens from Tabasco, México. Parasitology 2 40588766
2025 Isolation and molecular characterization of Toxoplasma gondii from naturally infected seabirds on the southern coast of Santa Catarina state, Brazil. Parasitology research 2 41081955
2025 Dolphins share Toxoplasma gondii Type II genotypes with terrestrial animals: Evidence of terrestrial T. gondii contamination in marine environments. Veterinary parasitology 2 40048863
2025 A Structural In Silico Analysis of Novel Epitopes from Toxoplasma gondii Proteins for the Serodiagnosis of Toxoplasmosis. International journal of molecular sciences 2 40429830
2026 Association between Toxoplasma gondii IgG seropositivity and schizophrenia: A case-control study in Colombia. Schizophrenia research 1 41833571
2025 A chemiluminescence immunoassay for detection of Toxoplasma gondii antibody in porcine based on GRA6 and SAG1. Veterinary parasitology 1 40023974
2025 First molecular characterization of Toxoplasma gondii and molecular analysis of Neospora caninum in American mink (Neogale vison) introduced in Argentina. Research in veterinary science 1 41109155
2025 Design of a Multi-epitope Antigen for Toxoplasmosis Diagnosis: An Immunoinformatics Approach. Acta parasitologica 1 40924315
2026 Seroepidemiology, clinical correlates, and GRA6-based genotyping of Toxoplasma gondii among immunocompromised patients in northeastern Iran. Acta tropica 0 42114610
2026 An ELISA Using a T. gondii GRA6-Derived Peptide as Antigen Successfully Detected Ovine Toxoplasmosis. Acta parasitologica 0 41528606
2026 Toxoplasma gondii in slaughtered sheep: a study of parasite prevalence, isolation, genotyping, virulence, and potential health risks to butchers in India. Microbial pathogenesis 0 41687934
2026 Elevated Liver Enzymes and Genotype I of T. gondii Among Liver Cancer Patients: Evidence of a Potential Link. Asian Pacific journal of cancer prevention : APJCP 0 41569205
2026 First Case of Congenital Toxoplasmosis After Maternal Reinfection in Colombia: Serotyping Evidence of Reinfection by Different Strains. The Pediatric infectious disease journal 0 42231089
2026 Bivalve mollusks as sentinels: Molecular detection of Toxoplasma gondii on Maranhão Island in northeastern Brazil. International journal for parasitology. Parasites and wildlife 0 42358338
2026 First report of viable Toxoplasma gondii isolation from African lions (Panthera leo): Evidence for their status as intermediate hosts. Food and waterborne parasitology 0 41675383
2025 Biological function and genotype identification of the isolated Toxoplasma gondii strain from human peripheral blood. Microbial pathogenesis 0 41093156
2025 Molecular detection and genetic characterization of Toxoplasma gondii in goats' milk and aborted goat kid tissues from Pakistan. Food and waterborne parasitology 0 41209691
2025 Phylogenetic study of the protozoan Toxoplasma gondii using cytochrome b and GRA20 genes. Archives of Razi Institute 0 42058244