Affinage · Toxoplasma gondii

GRA7

dense granule protein GRA7 · UniProt A0A125YI90

Annotated
2026-09-07
98 papers in source corpus 19 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRA7 is a Toxoplasma gondii dense granule protein secreted after host cell invasion into the parasitophorous vacuole (PV), where it traffics via the intravacuolar network to the PV membrane (PVM) and integrates as an integral membrane protein through a hydrophobic membrane anchor (residues 181–202) (PMID:9566518, PMID:9566517, PMID:9815283, PMID:12048027). It is expressed across all infectious life stages, uniquely including the enteric coccidian stages that lack other dense granule proteins, and persists at the cyst periphery during chronic infection (PMID:10503251, PMID:15003495, PMID:31941814). At the PVM, GRA7 decorates microtubule-based tubular invaginations and acts as a tubulogenic "garrote" that sequesters host endo-lysosomes within the vacuolar space (PMID:16630815), and it assembles into high-molecular-weight oligomeric complexes with other GRA proteins including GRA2, GRA3, GRA5, and GRA6 (PMID:17959262). GRA7 is a central effector of a virulence complex with the rhoptry proteins ROP2/ROP4, ROP5, and the active kinase ROP18: it associates with the PVM through direct binding to ROP5 and directly binds the GTP-loaded Irga6 dimer in a GTP-dependent manner, driving Irga6 phosphorylation, polymerization, and disassembly to protect the PVM from IRG-mediated destruction (PMID:18809661, PMID:24390541, PMID:26247512). Genetic epistasis places GRA7 and ROP18 in the same pathway, and loss of GRA7 (with ROP5/ROP18) permits IRG recruitment, PV disruption, and increased MHC-I presentation of parasite antigens to CD8+ T cells (PMID:24390541, PMID:31266861, PMID:31555296). GRA7 also engages host innate immune signaling, activating MyD88/TRAF6-dependent NF-κB proinflammatory responses through its C-terminal domain (PMID:26553469, PMID:32849602), and undergoes PKCα-mediated phosphorylation (Ser52, Ser135) that governs its interactions with ASC and phospholipase D1 in antimicrobial defense (PMID:28125719). GRA7 is required for normal chronic cyst wall maturation in vivo (PMID:31266861, PMID:31555296, PMID:31941814).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 High

    Establishing GRA7 as a secreted dense granule protein answered where it acts, defining its localization at the PV membrane and intravacuolar network after invasion.

    Evidence Immunoelectron microscopy, immunofluorescence, and biochemistry on tachyzoite- and bradyzoite-infected cells, plus immunogold trafficking analysis

    PMID:9566518 PMID:9566517 PMID:9815283

    Open questions at the time
    • Membrane topology and mode of PVM insertion not yet resolved
    • Functional consequence of secretion not addressed
  2. 1999 Medium

    Documenting GRA7 expression across all life-cycle and enteric stages distinguished it from GRA1–6 and implicated it in every infectious form.

    Evidence Immunocytochemistry with stage-specific markers and electron microscopy in cat and intermediate-host infections

    PMID:10503251

    Open questions at the time
    • Stage-specific function not defined
    • Reduced cyst-wall staining in bradyzoites left unexplained
  3. 2002 High

    Biochemical characterization resolved GRA7 as an integral membrane protein with a defined anchor and linked its expression to parasite virulence.

    Evidence Triton X-114 partitioning, subcellular fractionation, and flow cytometry, plus correlation with an attenuated variant

    PMID:12048027

    Open questions at the time
    • Nature of post-exocytosis modifications not identified
    • Mechanistic basis of the virulence correlation not established
  4. 2004 Medium

    Confirmation of GRA7 expression in tachyzoites, bradyzoites, and merozoites reinforced its unique pan-stage distribution relative to other GRAs.

    Evidence Immunocytochemistry with marker panel, electron microscopy, and in vivo infections

    PMID:15003495

    Open questions at the time
    • Does not test function in any stage
    • Cyst-wall staining variability unresolved
  5. 2006 High

    Discovery of GRA7-decorated microtubule tubules answered how the PV manipulates host endocytic organelles, defining a tubulogenic sequestration role.

    Evidence Immunoelectron and fluorescence microscopy, fractionation, and live imaging of host endo-lysosome recruitment to the PV

    PMID:16630815

    Open questions at the time
    • Molecular mechanism of tubule formation by GRA7 not defined
    • Contribution of sequestration to nutrient acquisition not quantified
  6. 2007 High

    Affinity purification defined GRA7 as a member of oligomeric GRA complexes, showing how dense granule proteins assemble before and after membrane insertion.

    Evidence HA-FLAG affinity purification from knockout-complemented parasites with reciprocal pulls and immunoblot

    PMID:17959262

    Open questions at the time
    • Stoichiometry and structural arrangement of complexes unknown
    • Functional role of GRA7 within these complexes not tested
  7. 2008 High

    Detection of host-dependent phosphorylation and rhoptry-protein association linked GRA7 to ROP2/ROP4 in host-cytosolic strands, foreshadowing its virulence-complex role.

    Evidence Immunoprecipitation, immunofluorescence colocalization, and comparison of extracellular vs. intracellular parasite phosphorylation

    PMID:18809661

    Open questions at the time
    • Kinase responsible for phosphorylation not identified here
    • Functional significance of GRA7-ROP2/ROP4 strands not established
  8. 2014 High

    Genetic epistasis and direct binding assays revealed GRA7's core effector mechanism: disabling the host Irga6 GTPase to protect the PVM.

    Evidence Single and double gra7/rop18 knockouts, in vivo virulence assays, direct GRA7–Irga6 dimer binding assay, and IFN-γ macrophage clearance in RH strain

    PMID:24390541

    Open questions at the time
    • Structural basis of GRA7–Irga6 recognition not resolved
    • Whether GRA7 targets IRGs beyond Irga6 not addressed here
  9. 2015 High

    Defining GRA7 as a ROP5-binding component of the ROP5/ROP18 kinase complex answered how GRA7 is recruited to the PVM and regulates Irga6-specific inactivation.

    Evidence Reciprocal co-IP, genetic deletion, Irga6 phosphorylation and IRG recruitment quantification, and in vivo virulence

    PMID:26247512

    Open questions at the time
    • Why GRA7 is Irga6-specific and not broader across IRGs not explained mechanistically
    • Strain background of this study unspecified
  10. 2015 High

    Mapping the GRA7 C-terminal domain to TRAF6 defined a distinct role activating host MyD88/NF-κB proinflammatory signaling.

    Evidence Co-IP, GRA7-V domain-deletion mapping, TRAF6 ubiquitination assay, and cytokine measurement in MyD88-knockout macrophages

    PMID:26553469

    Open questions at the time
    • How PVM-integral GRA7 accesses cytosolic TRAF6 not resolved
    • In vivo relevance of the TRAF6 axis not established here
  11. 2017 High

    Identification of PKCα phosphosites (Ser52, Ser135) governing GRA7 binding to ASC and PLD1 connected GRA7 phosphorylation to inflammasome and phago-lysosomal antimicrobial defense.

    Evidence Co-IP, phosphosite mutagenesis, PLD1 enzyme activity, phago-lysosomal maturation, and inflammasome activation assays

    PMID:28125719

    Open questions at the time
    • Whether these host-defense functions operate during Toxoplasma infection itself vs. heterologous contexts not delineated
    • Physiological trigger for PKCα phosphorylation not defined
  12. 2019 High

    Deletion studies in the type II Pru strain established GRA7's requirement for chronic cyst development and its role in suppressing MHC-I antigen presentation.

    Evidence Genetic deletion of PVM-associated GRAs, in vivo chronic infection, MHC-I presentation and IRG recruitment assays in Pru and RH

    PMID:31266861 PMID:31555296

    Open questions at the time
    • Mechanism linking PVM integrity to cyst development not defined
    • Relative contributions of GRA7 vs. co-deleted GRAs not fully separated
  13. 2020 High

    Reporter and deletion analyses positioned GRA7 alongside GRA14/GRA15 as a contributor to host NF-κB/RelA activation that restrains parasite expansion.

    Evidence NF-κB luciferase reporter, Δgra7/Δgra14/Δgra15 deletions, RelA translocation, RNA-seq, cytokine and in vivo virulence assays in Pru

    PMID:32849602

    Open questions at the time
    • Direct molecular partner of GRA7 driving RelA translocation not identified
    • Relationship to the TRAF6/MyD88 axis not reconciled
  14. 2020 High

    Time-course imaging showed GRA7 localizing to the cyst periphery from early differentiation and persisting in the mature cyst membrane, supporting PVM-to-cyst-membrane continuity.

    Evidence Live imaging and immunofluorescence during in vitro differentiation, saponin permeabilization, and genetic deletion with cyst-wall accumulation readout in Pru

    PMID:31941814

    Open questions at the time
    • Molecular contribution of GRA7 to cyst-wall protein deposition not mechanistically defined
    • Differential saponin extraction of GRA5 vs. GRA7 unexplained
  15. 2020 Medium

    Characterization of GRA60 clarified that GRA7 is one of several parallel effectors (GRA7, GRA60, ROP5/ROP17/ROP18) resisting IRG-mediated PVM disruption.

    Evidence GRA60 deletion, IRG recruitment assay, GRA60-ROP18 co-IP, and in vivo virulence in RH

    PMID:33040458

    Open questions at the time
    • How the multiple IRG-resistance effectors are coordinated at the PVM not resolved
    • GRA7's role here is corroborative rather than primary
  16. 2025 Medium

    Detection of GRA7 in neuron-derived extracellular vesicles and in astrocyte nuclei suggested a route for GRA7 dissemination and host-cell reprogramming beyond the infected cell.

    Evidence LC-MS/MS EV proteomics, nanoparticle tracking, electron microscopy, immunofluorescence of GRA7 in astrocyte nuclei, and astrocyte RNA-seq

    PMID:40523037

    Open questions at the time
    • Not yet independently replicated
    • Mechanism of GRA7 nuclear entry and direct causal role in astrocyte gene changes not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of GRA7's PVM membrane insertion and its direct engagement of Irga6, and how a single protein integrates tubulogenesis, IRG neutralization, NF-κB activation, and cyst maturation, remain unresolved.
  • No structural model of GRA7 or its complexes
  • Mechanistic coupling between GRA7's distinct functions unknown
  • How host phosphorylation states switch GRA7 between roles not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
ASC (HOST)GRA1GRA2GRA3GRA5GRA6IRGA6 (HOST)MYD88 (HOST)PKCΑ (HOST)PLD1 (HOST)ROP18ROP2ROP4ROP5TRAF6 (HOST)
Complex memberships
GRA7–Irga6 (GTP-loaded dimer) complexOligomeric dense granule complex with GRA2, GRA3, GRA5, GRA6 (GRA7 partner)PVM virulence complex with ROP5, ROP18, ROP2/ROP4 (pseudokinase ROP8/ROP2)

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 GRA7 acts as a tubulogenic protein that decorates microtubule-based invaginations of the parasitophorous vacuole membrane (PVM), functioning like a garrote to sequester host endo-lysosomes within the vacuolar space. The parasite actively recruits host microtubules to the PV, and these tubular conduits decorated by GRA7 mediate unidirectional transport and sequestration of host endocytic organelles. Immunoelectron microscopy, fluorescence microscopy, subcellular fractionation, live imaging of host endo-lysosome recruitment to PV Cell High 16630815
1998 GRA7 (p29) is a dense granule protein that, after host cell invasion, is secreted into the parasitophorous vacuole (PV) and associates with the PV membrane and intravacuolar network. In bradyzoite-infected cells, GRA7 is present in the host cell cytoplasm and is released into culture supernatant, suggesting excretion from cyst-bearing cells. The protein contains a putative N-terminal signal peptide and a C-terminal hydrophobic transmembrane domain, and is expressed in all three intraspecies subgroups. Immunoelectron microscopy, immunofluorescence, Northern blot, ELISA, protein sequencing from tryptic peptides, genomic DNA amplification Molecular and biochemical parasitology High 9566517 9566518
1998 Ultrastructural immunolocalization demonstrated that GRA7 (P29) traffics from dense granules via the intravacuolar network to the PVM after tachyzoite invasion, associating with the parasite membrane complex, tubular elements of the intravacuolar network, and the parasitophorous vacuolar membrane. Immunogold electron microscopy on thin sections using monoclonal antibody 5-241-178 The journal of histochemistry and cytochemistry High 9815283
2002 GRA7 is exclusively membrane-associated in parasites and infected host cells. Triton X-114 partitioning demonstrates GRA7 is an integral membrane protein, with the hydrophobic stretch from amino acids 181–202 serving as a membrane anchor. GRA7 is detected on the surface of intact host cells (originating intracellularly), and additional slower-migrating modified forms of GRA7 appear in membranous fractions from infected host cells, indicating post-exocytosis modification. GRA7 expression level correlates with T. gondii virulence, with a massive decrease in GRA7 synthesis in an in vitro-attenuated variant. GRA7-specific antibodies are present in cerebrospinal fluid during chronic infection, consistent with a role at the parasite-host interface. Proteome analysis, immunoblot, subcellular fractionation, Triton X-114 partitioning, flow cytometry Microbes and infection High 12048027
1999 GRA7 is expressed in all infectious life cycle stages of T. gondii (tachyzoite, bradyzoite, merozoite, sporozoite) and is uniquely the only dense granule protein also expressed in enteric (coccidian) stages in the cat gut. During tachyzoite development, GRA7 is secreted and associates with the parasitophorous vacuole. In bradyzoites within mature cysts, GRA7 staining of the cyst wall is reduced compared to tachyzoites. In enteric forms, GRA7 strongly labels PV-containing early asexual and sexual stages. This stage-specific pattern differentiates GRA7 from GRA1–6. Immunocytochemistry with stage-specific markers (SAG1, BAG1), electron microscopy, in vivo infection model (cat and intermediate host) Parasitology Medium 10503251
2007 GRA proteins, including GRA7, form high-molecular-weight oligomeric complexes within the parasite dense granules and within the PV soluble fraction. Affinity purification of HA-FLAG-tagged GRA2 and GRA5 revealed that GRA3, GRA6, and GRA7 are major partners in these complexes. After insertion into PV membranes, GRA2 associates with GRA5 and GRA7, while GRA5 associates with GRA7 only, suggesting progressive loss of partners upon membrane insertion. Affinity chromatography (HA-FLAG tag purification) of knockout parasites complemented with tagged GRA2 or GRA5, conventional chromatography, immunoblot Molecular and biochemical parasitology High 17959262
2008 GRA7 is phosphorylated in infected host cells but not in extracellular parasites, indicating host cell-dependent phosphorylation. Within 10 min of invasion, GRA7 appears in strand-like structures in the host cytosol that also contain rhoptry proteins. Independently of its phosphorylation state, GRA7 associates with rhoptry proteins ROP2 and ROP4 in infected host cells. GRA7 strands also contain the dense granule proteins GRA1 and GRA3. Immunoprecipitation, immunofluorescence, phosphorylation analysis of extracellular vs. intracellular parasites, co-localization studies Infection and immunity High 18809661
2014 GRA7 exists in a complex with the pseudokinases ROP8/ROP2 and the active kinase ROP18 at the PVM. Individual deletion of gra7 or rop18 partially attenuates virulence in mice, while the double gra7/rop18 mutant is avirulent, placing GRA7 and ROP18 in the same pathway. GRA7 directly binds the active GTP-bound dimer of immunity-related GTPase a6 (Irga6) in a GTP-dependent manner, leading to enhanced Irga6 polymerization, rapid turnover, and eventual disassembly. Increased IRG recruitment and parasite clearance occur in IFN-γ-activated macrophages lacking GRA7 and ROP18. Genetic deletion (single and double knockout), in vivo virulence assays in mice, direct binding assay (GRA7 to Irga6 dimer), IFN-γ-activated macrophage clearance assay, epistasis analysis Proceedings of the National Academy of Sciences of the United States of America High 24390541
2015 GRA7 is an additional component of the ROP5/ROP18 kinase complex and associates with the PVM through direct binding to ROP5. Absence of GRA7 results in reduced phosphorylation of Irga6, increased vacuolar IRG protein amounts, and attenuated virulence. GRA7 is strictly an Irga6-specific virulence effector (not targeting other IRG family members), functioning as a regulator for ROP18-specific inactivation of Irga6. Co-immunoprecipitation, genetic deletion analysis, Irga6 phosphorylation assay, in vivo virulence assay, IRG recruitment quantification Cellular microbiology High 26247512
2015 GRA7 induces MyD88-dependent signaling through TRAF6 activation and ROS production, leading to NF-κB-mediated proinflammatory responses in macrophages. GRA7 physically associates with TRAF6 via MyD88. The C-terminal domain of GRA7 (GRA7-V) is sufficient for interaction with and ubiquitination of the RING domain of TRAF6, enabling inflammatory cytokine production. PKCα-independent ROS generation and TRAF6 activation are mutually dependent on GRA7/MyD88 signaling. Co-immunoprecipitation (GRA7-TRAF6 interaction), domain-deletion mapping (GRA7-V), ubiquitination assay, cytokine measurement, MyD88-knockout macrophages Infection and immunity High 26553469
2017 PKCα-mediated phosphorylation of GRA7 at Ser52 (GRA7-I domain) regulates GRA7 interaction with the PYD domain of ASC (apoptosis-associated speck-like protein), enabling oligomerization and inflammasome activation for antimicrobial defense against Mycobacterium tuberculosis. GRA7-III domain interacts with the PX domain of phospholipase D1 (PLD1) in a Ser135 phosphorylation-dependent manner (also via PKCα), facilitating PLD1 enzyme activity and phago-lysosomal maturation, contributing to antimicrobial activity. Co-immunoprecipitation (GRA7-ASC, GRA7-PLD1), phosphorylation-site mutagenesis (Ser52, Ser135), PLD1 enzyme activity assay, phago-lysosomal maturation assay, inflammasome activation assay PLoS pathogens High 28125719
2019 Deletion of PVM-associated GRA7 (along with GRA3, GRA8, GRA14) in the type II Prugniaud strain induces severe defects in chronic cyst development in vivo without affecting in vitro growth rate or in vitro differentiation. GRA7 deletion parasites show reduced acute virulence. GRA7 (along with ROP5, ROP18) suppresses MHC-I antigen presentation of PV-localized parasite antigens to CD8+ T cells, with suppression correlated to prevention of PV disruption by IFN-γ-activated host IRG effectors. Genetic deletion in type II Pru strain, in vivo chronic infection model (mouse), in vitro differentiation assay, MHC-I antigen presentation assay, IRG recruitment assay mBio High 31266861 31555296
2020 GRA7 and GRA14 (but not GRA15 alone) are partially involved in NF-κB activation; all three (GRA7, GRA14, GRA15) contribute to nuclear translocation of RelA. Deletion of GRA7, GRA14, and GRA15 decreases IL-6 levels in macrophages and downregulates NF-κB-mediated gene expression. Luciferase reporter assays confirm GRA7 overexpression activates NF-κB-dependent transcription. Deletion of GRA7 in the type II Pru strain increases parasite virulence, suggesting GRA7-induced host NF-κB immunity limits parasite expansion. Luciferase reporter assay (NF-κB), genetic deletion (Δgra7, Δgra14, Δgra15), RelA nuclear translocation assay, RNA-seq, cytokine measurement, in vivo virulence assay Frontiers in immunology High 32849602
2020 GRA5 and GRA7 localize to the cyst periphery as early as 6 h after in vitro differentiation and remain at the cyst membrane and cyst wall region throughout cyst maturation (up to day 10), supporting the model that the PVM remains intact and develops into the cyst membrane. In mature cysts, saponin permeabilization selectively removes GRA5 but not GRA7 from the cyst membrane. Deletion of PVM-localized GRAs including GRA7 reduces the rate of cyst wall protein accumulation at the cyst periphery. Live imaging and immunofluorescence of GRA5/GRA7 during in vitro differentiation, saponin permeabilization assay, genetic deletion of individual GRAs with cyst wall protein accumulation readout mSphere High 31941814
2004 GRA7 is expressed in tachyzoites, bradyzoites, and coccidian/enteric stages (merozoites), whereas GRA1–6 are absent in merozoites and enteric stages. In tachyzoites, GRA7 extensively labels the PV; in bradyzoites within cysts, the cyst wall shows variable staining. This unique expression in all stages is reflected in the differences in PV structure observed by electron microscopy across life cycle stages. Immunocytochemistry with panel of molecular markers, electron microscopy, in vivo infections in cat and intermediate host International journal for parasitology Medium 15003495
2025 GRA7 protein is packaged into extracellular vesicles (EVs) released from Toxoplasma-infected neurons, and GRA7 can be observed within intracellular EVs and in the nuclei of GRA7+ EV-containing astrocytes after incubation with infected-neuron EVs. EVs from infected neurons altered astrocyte gene expression toward pro-inflammatory signatures and downregulated GLT-1 glutamate transporter expression. LC-MS/MS proteomic characterization of EVs, immunofluorescence (GRA7 in astrocyte nuclei), nanoparticle tracking analysis, transmission electron microscopy, RNA-seq of astrocytes PLoS pathogens Medium 40523037
2020 GRA60, a novel dense granule effector at the vacuolar space and PVM, contributes to resistance to IRG recruitment independently of GRA7. GRA60 is found associated with ROP18. Deletion of GRA60 in an RHΔrop5 background leads to IRG recruitment comparable to single knockouts, demonstrating GRA60 and ROP5 act in the same pathway. This study contextualizes GRA7 as one member of a broader virulence complex (GRA7, ROP5, ROP17, ROP18) resisting IRG-mediated PVM disruption. Genetic deletion of GRA60, IRG recruitment assay, co-immunoprecipitation (GRA60-ROP18), in vivo virulence assay Cellular microbiology Medium 33040458

Source papers

Stage 0 corpus · 98 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Toxoplasma gondii sequesters lysosomes from mammalian hosts in the vacuolar space. Cell 263 16630815
2000 Recombinant antigens to detect Toxoplasma gondii-specific immunoglobulin G and immunoglobulin M in human sera by enzyme immunoassay. Journal of clinical microbiology 132 10699010
2000 DNA vaccination with genes encoding Toxoplasma gondii antigens GRA1, GRA7, and ROP2 induces partially protective immunity against lethal challenge in mice. Infection and immunity 129 10603366
2004 Use of molecular and ultrastructural markers to evaluate stage conversion of Toxoplasma gondii in both the intermediate and definitive host. International journal for parasitology 118 15003495
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
2014 Toxoplasma GRA7 effector increases turnover of immunity-related GTPases and contributes to acute virulence in the mouse. Proceedings of the National Academy of Sciences of the United States of America 104 24390541
2004 Usefulness of Toxoplasma gondii-specific recombinant antigens in serodiagnosis of human toxoplasmosis. Journal of clinical microbiology 98 15071048
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
2005 Seroreactivity to and avidity for recombinant antigens in toxoplasmosis. Clinical and diagnostic laboratory immunology 89 16085916
1999 Evaluation of recombinant dense granule antigen 7 (GRA7) of Toxoplasma gondii for detection of immunoglobulin G antibodies and analysis of a major antigenic domain. Clinical and diagnostic laboratory immunology 83 9874659
1998 GRA7, an excretory 29 kDa Toxoplasma gondii dense granule antigen released by infected host cells. Molecular and biochemical parasitology 83 9566518
2008 The Toxoplasma gondii dense granule protein GRA7 is phosphorylated upon invasion and forms an unexpected association with the rhoptry proteins ROP2 and ROP4. Infection and immunity 78 18809661
1998 Identification and heterologous expression of a new dense granule protein (GRA7) from Toxoplasma gondii. Molecular and biochemical parasitology 76 9566517
2019 Toxoplasma gondii Parasitophorous Vacuole Membrane-Associated Dense Granule Proteins Orchestrate Chronic Infection and GRA12 Underpins Resistance to Host Gamma Interferon. mBio 75 31266861
2006 Chimeric antigens of Toxoplasma gondii: toward standardization of toxoplasmosis serodiagnosis using recombinant products. Journal of clinical microbiology 73 16757610
2013 Toxoplasma gondii prevalence in food animals and rodents in different regions of China: isolation, genotyping and mouse pathogenicity. Parasites & vectors 72 24330536
2009 Genetic characterization of Toxoplasma gondii from wild boar (Sus scrofa) in France. Veterinary parasitology 66 19592170
2015 The Toxoplasma gondii rhoptry protein ROP18 is an Irga6-specific kinase and regulated by the dense granule protein GRA7. Cellular microbiology 65 26247512
2003 Use of an immunoglobulin G avidity assay based on recombinant antigens for diagnosis of primary Toxoplasma gondii infection during pregnancy. Journal of clinical microbiology 65 14662919
2007 An enhanced GRA1-GRA7 cocktail DNA vaccine primes anti-Toxoplasma immune responses in pigs. Vaccine 63 18221825
2013 Development of an immunochromatographic assay based on dense granule protein 7 for serological detection of Toxoplasma gondii infection. Clinical and vaccine immunology : CVI 60 23408523
2007 GRA7 provides protective immunity in cocktail DNA vaccines against Toxoplasma gondii. Parasite immunology 58 17727568
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
2003 Molecular dissection of the human B-cell response against Toxoplasma gondii infection by lambda display of cDNA libraries. International journal for parasitology 54 12633654
2006 Usefulness of Toxoplasma gondii recombinant antigens (GRA1, GRA7 and SAG1) in an immunoglobulin G avidity test for the serodiagnosis of toxoplasmosis. Parasitology research 49 16896649
2015 Toxoplasma gondii: Vaccination with a DNA vaccine encoding T- and B-cell epitopes of SAG1, GRA2, GRA7 and ROP16 elicits protection against acute toxoplasmosis in mice. Vaccine 48 26518401
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
2006 Toxoplasma gondii: an evaluation of diagnostic value of recombinant antigens in a murine model. Experimental parasitology 44 16707125
2013 Identification of differentially expressed proteins in sulfadiazine resistant and sensitive strains of Toxoplasma gondii using difference-gel electrophoresis (DIGE). International journal for parasitology. Drugs and drug resistance 42 24533291
2012 Induction of protective immune responses by a multiantigenic DNA vaccine encoding GRA7 and ROP1 of Toxoplasma gondii. Clinical and vaccine immunology : CVI 42 22419676
2003 High yield expression and single-step purification of Toxoplasma gondii SAG1, GRA1, and GRA7 antigens in Escherichia coli. Protein expression and purification 42 12509997
2002 Expression variance, biochemical and immunological properties of Toxoplasma gondii dense granule protein GRA7. Microbes and infection 41 12048027
2015 Toxoplasma gondii GRA7-Induced TRAF6 Activation Contributes to Host Protective Immunity. Infection and immunity 40 26553469
2008 Toxoplasma gondii: enzyme-linked immunosorbent assay using different fragments of recombinant microneme protein 1 (MIC1) for detection of immunoglobulin G antibodies. Experimental parasitology 40 18207143
2010 Non-archetypal Type II-like and atypical strains of Toxoplasma gondii infecting marsupials of Australia. International journal for parasitology 39 20346947
2019 A systematic review on the role of GRA proteins of Toxoplasma gondii in host immunization. Journal of microbiological methods 38 31442457
2013 Atypical strain of Toxoplasma gondii causing fatal reactivation after hematopoietic stem cell transplantion in a patient with an underlying immunological deficiency. Journal of clinical microbiology 38 23761151
2020 Toxoplasma gondii Dense Granule Proteins 7, 14, and 15 Are Involved in Modification and Control of the Immune Response Mediated via NF-κB Pathway. Frontiers in immunology 37 32849602
2016 Seroprevalence and epidemiology of Toxoplasma gondii in farm animals in different regions of Egypt. Veterinary parasitology, regional studies and reports 37 31014492
2010 Functional characterization of in vivo effector CD4(+) and CD8(+) T cell responses in acute Toxoplasmosis: an interplay of IFN-gamma and cytolytic T cells. Vaccine 37 20117266
2020 Isolation and genetic characterization of Toxoplasma gondii in Spanish sheep flocks. Parasites & vectors 36 32758283
2008 High-level expression of SAG1 and GRA7 gene of Toxoplasma gondii (Izatnagar isolate) and their application in serodiagnosis of goat toxoplasmosis. Veterinary parasitology 36 18495348
2007 Purification of Toxoplasma dense granule proteins reveals that they are in complexes throughout the secretory pathway. Molecular and biochemical parasitology 36 17959262
2012 Production and evaluation of Toxoplasma gondii recombinant GRA7 for serodiagnosis of human infections. The Korean journal of parasitology 35 22949752
2012 Enhancement of protective immune responses induced by Toxoplasma gondii dense granule antigen 7 (GRA7) against toxoplasmosis in mice using a prime-boost vaccination strategy. Vaccine 35 22789504
2009 Induction of partial protection against infection with Toxoplasma gondii genotype II by DNA vaccination with recombinant chimeric tachyzoite antigens. Vaccine 34 19368791
1998 Quantitative immunolocalization of a P29 protein (GRA7), a new antigen of toxoplasma gondii. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 32 9815283
2020 Toxoplasma gondii induces robust humoral immune response against cyst wall antigens in chronically infected animals and humans. Microbial pathogenesis 31 33232762
2015 Immunodiagnosis and molecular validation of Toxoplasma gondii-recombinant dense granular (GRA) 7 protein for the detection of toxoplasmosis in patients with cancer. Microbiological research 31 26805618
2009 Selection of polymorphic peptides from GRA6 and GRA7 sequences of Toxoplasma gondii strains to be used in serotyping. Clinical and vaccine immunology : CVI 31 19494084
2011 Toxoplasma gondii HLA-B*0702-restricted GRA7(20-28) peptide with adjuvants and a universal helper T cell epitope elicits CD8(+) T cells producing interferon-γ and reduces parasite burden in HLA-B*0702 mice. Human immunology 30 22027386
2012 Recombinant proteins from new constructs of SAG1 and GRA7 sequences and their usefulness to detect acute toxoplasmosis. Tropical biomedicine 29 22543613
2017 Toxoplasma gondii GRA7-Targeted ASC and PLD1 Promote Antibacterial Host Defense via PKCα. PLoS pathogens 27 28125719
2014 Evaluation of recombinant granule antigens GRA1 and GRA7 for serodiagnosis of Toxoplasma gondii infection in dogs. BMC veterinary research 27 25016474
2009 Bilateral retinochoroiditis caused by an atypical strain of Toxoplasma gondii. The British journal of ophthalmology 27 19666926
2020 Toxoplasma gondii Parasitophorous Vacuole Membrane-Associated Dense Granule Proteins Regulate Maturation of the Cyst Wall. mSphere 26 31941814
2017 Seroprevalence, isolation and co-infection of multiple Toxoplasma gondii strains in individual bobcats (Lynx rufus) from Mississippi, USA. International journal for parasitology 26 28238868
1999 In vivo expression and distribution of dense granule protein 7 (GRA7) in the exoenteric (tachyzoite, bradyzoite) and enteric (coccidian) forms of Toxoplasma gondii. Parasitology 26 10503251
2019 Serotyping of Toxoplasma gondii Infection Using Peptide Membrane Arrays. Frontiers in cellular and infection microbiology 25 31850240
2016 Evaluation of recombinant antigens in combination and single formula for diagnosis of feline toxoplasmosis. Experimental parasitology 25 27876472
2014 Evaluation of an indirect ELISA using recombinant granule antigen Gra7 for serodiagnosis of Toxoplasma gondii infection in cats. The Journal of parasitology 25 25216850
2013 Toxoplasma gondii: immune response and protective efficacy induced by ROP16/GRA7 multicomponent DNA vaccine with a genetic adjuvant B7-2. Human vaccines & immunotherapeutics 25 24096573
2013 Seroprevalence of toxoplasmosis, toxocariasis and cysticercosis in a rural settlement, São Paulo State, Brazil. Pathogens and global health 25 23683335
2020 Toxoplasma gondii GRA60 is an effector protein that modulates host cell autonomous immunity and contributes to virulence. Cellular microbiology 24 33040458
2018 Discovery of new Toxoplasma gondii antigenic proteins using a high throughput protein microarray approach screening sera of murine model infected orally with oocysts and tissue cysts. Parasites & vectors 24 29973272
2015 Prime-boost vaccination with toxoplasma lysate antigen, but not with a mixture of recombinant protein antigens, leads to reduction of brain cyst formation in BALB/c mice. PloS one 23 26010355
2011 Prevalence of specific IgG-antibodies against Toxoplasma gondii in domestic turkeys determined by kinetic ELISA based on recombinant GRA7 and GRA8. Veterinary parasitology 23 21524853
2009 Comparison of immune response in sheep immunized with DNA vaccine encoding Toxoplasma gondii GRA7 antigen in different adjuvant formulations. Experimental parasitology 23 19962376
2022 Designing a Multi-Epitope Vaccine against Toxoplasma gondii: An Immunoinformatics Approach. Vaccines 21 36146470
2019 Development, optimization, and validation of an in-house Dot-ELISA rapid test based on SAG1 and GRA7 proteins for serological detection of Toxoplasma gondii infections. Infection and drug resistance 21 31695442
2019 Rhoptry and Dense Granule Secreted Effectors Regulate CD8+ T Cell Recognition of Toxoplasma gondii Infected Host Cells. Frontiers in immunology 21 31555296
2015 Evaluation of an indirect ELISA using recombinant granule antigen GRA1, GRA7 and soluble antigens for serodiagnosis of Toxoplasma gondii infection in chickens. Research in veterinary science 21 25975627
2014 Evidence for genetic diversity of Toxoplasma gondii in selected intermediate hosts in Serbia. Comparative immunology, microbiology and infectious diseases 21 24698636
2012 Toxoplasma gondii antigens recognized by IgG antibodies differ between mice with and without active proliferation of tachyzoites in the brain during the chronic stage of infection. Infection and immunity 21 22851753
2011 IFN-γ expression and infectivity of Toxoplasma infected tissues are associated with an antibody response against GRA7 in experimentally infected pigs. Veterinary parasitology 21 21414723
2020 Serological diagnosis of Toxoplasma gondii: analysis of false-positive IgG results and implications. Parasite (Paris, France) 19 32031519
2023 Protective efficacy of Toxoplasma gondii GRA12 or GRA7 recombinant proteins encapsulated in PLGA nanoparticles against acute Toxoplasma gondii infection in mice. Frontiers in cellular and infection microbiology 9 37502604
2024 The Development of Toxoplasma gondii Recombinant Trivalent Chimeric Proteins as an Alternative to Toxoplasma Lysate Antigen (TLA) in Enzyme-Linked Immunosorbent Assay (ELISA) for the Detection of Immunoglobulin G (IgG) in Small Ruminants. International journal of molecular sciences 8 38673969
2025 IL-24 Is a Promising Molecular Adjuvant for Enhancing Protective Immunity Induced by DNA Vaccination Against Toxoplasma gondii. Microorganisms 7 40732170
2025 Immunization with plant-based vaccine expressing Toxoplasma gondii SAG1 fused to plant HSP90 elicits protective immune response in lambs. Acta tropica 6 39894243
2024 Comparison of immunological and molecular methods for laboratory diagnosis of ocular toxoplasmosis in blood, serum and tears in Brazil. PloS one 5 38319921
2025 Toxoplasma gondii infection of neurons alters the production and content of extracellular vesicles directing astrocyte phenotype and contributing to the loss of GLT-1 in the infected brain. PLoS pathogens 3 40523037
2025 Influenza virus-like particles presenting Toxoplasma gondii dense granule protein 7 protect mice from lethal ME49 challenge. Nanomedicine (London, England) 3 40799047
2024 A combination of GRA3, GRA6 and GRA7 peptides offer a useful tool for serotyping type II and III Toxoplasma gondii infections in sheep and pigs. Frontiers in cellular and infection microbiology 3 38720960
2024 Genetic characterization of Toxoplasma gondii strains isolated from humans living in İzmir, Türkiye. Indian journal of medical microbiology 3 38554777
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
2024 Comparison of the performance of SAG2, GRA6, and GRA7 for serological diagnosis of Toxoplasma gondii infection in cats. Frontiers in veterinary science 2 38898997
2025 Design of a Multi-epitope Antigen for Toxoplasmosis Diagnosis: An Immunoinformatics Approach. Acta parasitologica 1 40924315
2024 Comparative GRA6 and GRA7 for their Utility as Genetic Markers in the Genotyping of Cerebral Toxoplasmosis in Cerebrospinal Fluid. Acta parasitologica 1 39164550
2026 Dual transcriptomic analysis of Toxoplasma gondii infection in a human PBMC ex vivo model. Biochemical and biophysical research communications 0 42322816
2026 Multi-epitope mRNA vaccine and protein vaccine protect mice against Toxoplasma gondii. Parasites & vectors 0 42249505
2026 The immune-stimulating particle adjuvant (ISPA) as a versatile adjuvant platform for recombinant vaccines against chronic Toxoplasma gondii infection. Acta tropica 0 42336023
2026 Seroprevalence, Associated Factors, and Molecular Detection of Toxoplasma gondii Infection in Brazilian Gold Miners Working Informally in French Guiana. Journal of tropical medicine 0 42005300
2025 Molecular detection of Toxoplasma gondii in wild oysters and seawater on the southeast coast of South Korea. Food microbiology 0 41136142
2025 A comprehensive multi-epitope recombinant protein strategy for accurate serological detection of Toxoplasma gondii infection. Medical microbiology and immunology 0 41428119
2025 Functionality of Toxoplasma gondii antibodies in a population of Beninese pregnant women exposed to malaria. Scientific reports 0 40102442