ArticleGastroenterology2012
Binding of hepatitis A virus to its cellular receptor 1 inhibits T-regulatory cell functions in humans.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Outer membrane vesicles hijack TIM-1 for cellular uptake.PLoS pathogens · 2026Article
- Redefining the immune landscape of hepatitis A virus infection.Experimental & molecular medicine · 2025Review
- Molecular Basis for the Differential Function of HAVCR1 Mucin Variants.Biomedicines · 2024Article
- Hijacking host extracellular vesicle machinery by hepatotropic viruses: current understandings and future prospects.Journal of biomedical science · 2024Review
- Identification of New Prognostic Genes and Construction of a Prognostic Model for Lung Adenocarcinoma.Diagnostics (Basel, Switzerland) · 2023Article
- Improvement of the sepsis survival rate by adenosine 2a receptor antagonists depends on immune regulatory functions of regulatory T-cells.Frontiers in immunology · 2022Article
- Pathogenicity and virulence of hepatitis A virus.Virulence · 2021Review
- Exosome mimicry by a HAVCR1-NPC1 pathway of endosomal fusion mediates hepatitis A virus infection.Nature microbiology · 2020Article
- Host receptors: the key to establishing cells with broad viral tropism for vaccine production.Critical reviews in microbiology · 2020Review
- Adaptive Immune Responses in Hepatitis A Virus and Hepatitis E Virus Infections.Cold Spring Harbor perspectives in medicine · 2019Review
- Reply to Das et al., "TIM1 (HAVCR1): an Essential 'Receptor' or an 'Accessory Attachment Factor' for Hepatitis A Virus?"Journal of virology · 2019Article
- Murine Models of Hepatitis A Virus Infection.Cold Spring Harbor perspectives in medicine · 2019Review
- Understanding kidney injury molecule 1: a novel immune factor in kidney pathophysiology.American journal of translational research · 2019Review
- Natural History, Clinical Manifestations, and Pathogenesis of Hepatitis A.Cold Spring Harbor perspectives in medicine · 2018Review
- HAVCR1 (CD365) and Its Mouse Ortholog Are Functional Hepatitis A Virus (HAV) Cellular Receptors That Mediate HAV Infection.Journal of virology · 2018Article
- Determinants in the Ig Variable Domain of Human HAVCR1 (TIM-1) Are Required To Enhance Hepatitis C Virus Entry.Journal of virology · 2018Article
- Tumor Necrosis Factor-producing T-regulatory Cells Are Associated With Severe Liver Injury in Patients With Acute Hepatitis A.Gastroenterology · 2018Article
- Article
- Interplay of Regulatory T Cell and Th17 Cells during Infectious Diseases in Humans and Animals.Frontiers in immunology · 2017Review
- Immune responses and immunopathology in acute and chronic viral hepatitis.Nature reviews. Immunology · 2016Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsCD4+ T-regulatory (Treg) cells suppress immune responses and control self-tolerance and immunity to pathogens, cancer, and alloantigens. Most pathogens activate Treg cells to minimize immune-mediated tissue damage and prevent clearance, which promotes chronic infections. However, hepatitis A virus (HAV) temporarily inhibits Treg-cell functions. We investigated whether the interaction of HAV with its cellular receptor 1 (HAVCR1), a T-cell co-stimulatory molecule, inhibits the function of Treg cells to control HAV infection.
methodsWe studied the effects of HAV interaction with HAVCR1 on human T cells using binding, signal transduction, apoptosis, activation, suppression, cytokine production, and confocal microscopy analyses. Cytokines were analyzed in sera from 14 patients with HAV infection using bead arrays.
resultsHuman Treg cells constitutively express HAVCR1. Binding of HAV to HAVCR1 blocked phosphorylation of Akt, prevented activation of the T-cell receptor, and inhibited function of Treg cells. At the peak viremia, patients with acute HAV infection had no Treg-cell suppression function, produced low levels of transforming growth factor-β , which limited leukocyte recruitment and survival, and produced high levels of interleukin-22, which prevented liver damage.
conclusionsInteraction between HAV and its receptor HAVCR1 inhibits Treg-cell function, resulting in an immune imbalance that allows viral expansion with limited hepatocellular damage during early stages of infection-a characteristic of HAV pathogenesis. The mechanism by which HAV is cleared in the absence of Treg-cell function could be used as a model to develop anticancer therapies, modulate autoimmune and allergic responses, and prevent transplant rejection.
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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.