ArticleJournal of immunology (Baltimore, Md. : 1950)2013
GB virus C particles inhibit T cell activation via envelope E2 protein-mediated inhibition of TCR signaling.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Human Pegivirus Infection and Lymphoma Risk: A Systematic Review and Meta-analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Pooled it
- Downregulation of Cytokines and Chemokines by GB Virus C After Transmission Via Blood Transfusion in HIV-Positive Blood Recipients.The Journal of infectious diseases · 2015Trial
- Variation in antiviral immunity and inflammation pathways precedes HIV-1 infection in a high-risk African cohort.The Journal of clinical investigation · 2026Article
- Characterization of Serotype-Specific Dengue Virus T-Cell Inhibition.The Journal of infectious diseases · 2025Article
- Characterization of "Off-Target" Immune Modulation Induced by Live Attenuated Yellow Fever Vaccine.The Journal of infectious diseases · 2024Article
- Mycoplasma genitalium Protein of Adhesion Suppresses T Cell Activation via CypA-CaN-NFAT Pathway.Microbiology spectrum · 2023Article
- Review of human pegivirus: Prevalence, transmission, pathogenesis, and clinical implication.Virulence · 2022Review
- Human Pegivirus Type 1: A Common Human Virus That Is Beneficial in Immune-Mediated Disease?Frontiers in immunology · 2022Review
- Human pegivirus-1 replication influences NK cell reconstitution after allogeneic haematopoietic stem cell transplantation.Frontiers in immunology · 2022Article
- HIV-1 Tat-Induced Astrocytic Extracellular Vesicle miR-7 Impairs Synaptic Architecture.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Article
- Human Hepegivirus-1: Innocent Traveler, Helpful Symbiote, or Insidious Pathogen?Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Article
- Liquid Biopsy for the Diagnosis of Viral Hepatitis, Fatty Liver Steatosis, and Alcoholic Liver Diseases.International journal of molecular sciences · 2020Review
- Human Pegivirus infection and lymphoma risk and prognosis: a North American study.British journal of haematology · 2018Article
- Yellow Fever Virus, but Not Zika Virus or Dengue Virus, Inhibits T-Cell Receptor-Mediated T-Cell Function by an RNA-Based Mechanism.The Journal of infectious diseases · 2017Article
- Prevalence of human pegivirus-1 and sequence variability of its E2 glycoprotein estimated from screening donors of fetal stem cell-containing material.Virology journal · 2017Article
- Extracellular vesicles in liver disease and potential as biomarkers and therapeutic targets.Nature reviews. Gastroenterology & hepatology · 2017Review
- Hepatitis C virus infection inhibits a Src-kinase regulatory phosphatase and reduces T cell activation in vivo.PLoS pathogens · 2017Article
- Flow Virometry to Analyze Antigenic Spectra of Virions and Extracellular Vesicles.Journal of visualized experiments : JoVE · 2017Article
- Article
- GB virus type C E2 protein inhibits human immunodeficiency virus type 1 Gag assembly by downregulating human ADP-ribosylation factor 1.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Viruses enter into complex interactions within human hosts, leading to facilitation or suppression of each other's replication. Upon coinfection, GB virus C (GBV-C) suppresses HIV-1 replication in vivo and in vitro, and GBV-C coinfection is associated with prolonged survival in HIV-infected people. GBV-C is a lymphotropic virus capable of persistent infection. GBV-C infection is associated with reduced T cell activation in HIV-infected humans, and immune activation is a critical component of HIV disease pathogenesis. We demonstrate that serum GBV-C particles inhibited activation of primary human T cells. T cell activation inhibition was mediated by the envelope glycoprotein E2, because expression of E2 inhibited TCR-mediated activation of Lck. The region on the E2 protein was characterized and revealed a highly conserved peptide motif sufficient to inhibit TCR-mediated signaling. The E2 region contained a predicted Lck substrate site, and substitution of an alanine or histidine for the tyrosine reversed TCR-signaling inhibition. GBV-C E2 protein and a synthetic peptide representing the inhibitory amino acid sequence were phosphorylated by Lck in vitro. The synthetic peptide also inhibited TCR-mediated activation of primary human CD4(+) and CD8(+) T cells. Extracellular microvesicles from GBV-C E2-expressing cells contained E2 protein and inhibited TCR signaling in bystander T cells not expressing E2. Thus, GBV-C reduced global T cell activation via competition between its envelope protein E2 and Lck following TCR engagement. This novel inhibitory mechanism of T cell activation may provide new approaches for HIV and immunoactivation therapy.
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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.