ArticleThe Journal of clinical investigation2021
SIGLEC-3 (CD33) serves as an immune checkpoint receptor for HBV infection.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Druggable genome-wide Mendelian randomization identifies therapeutic targets for metabolic dysfunction-associated steatotic liver disease.Lipids in health and disease · 2025Pooled it
- CD33 and clusterin interact biophysically and genetically to modulate Alzheimer risk.Nature communications · 2026Article
- Crystal structure of the CD33/Fab-10C8 complex elucidates the mechanism of antibody antagonism in HBV-induced immunosuppression.Journal of biomedical science · 2026Article
- Mechanistic insight into complement C3 regulation during chronic HBV infection: effect on viral persistence and host immune response.Journal of biomedical science · 2026Article
- Beyond viral suppression: combining PEG-interferon with novel immunotherapies for functional cure of chronic hepatitis B.Frontiers in cellular and infection microbiology · 2026Review
- Research Progress on Mechanisms of Immune Tolerance Induced by Hepatitis B Surface Antigen in Chronic HBV Infection.Journal of immunology research · 2026Review
- Immunological and pathological roles of Siglecs: a molecular review.Frontiers in immunology · 2026Review
- HIV-induced sialoglycans on infected CD4+ T cells promote immune evasion from myeloid cell-mediated killing.Nature communications · 2025Article
- Increase of Inhibitory Siglec receptors on T cells mitigates severe immune reactions during acute viral infections.PNAS nexus · 2025Article
- Debates and progress in the management of intermediate-stage (BCLC stage B) hepatocellular carcinoma.iLIVER · 2025Review
- Association of CD33 genetic variants with neurocognitive profiles in chronic viral hepatitis.BJPsych open · 2025Article
- Single-cell and bulk transcriptome analysis unveils a ligand-receptor-based signature for prognostication and reveals that TREM1 controls the malignant behaviors of hepatocellular carcinoma.Acta biochimica et biophysica Sinica · 2025Article
- PGLYRP2 drives hepatocyte-intrinsic innate immunity by trapping and clearing hepatitis B virus.The Journal of clinical investigation · 2025Article
- Mechanistic and Therapeutic Implications of Protein and Lipid Sialylation in Human Diseases.International journal of molecular sciences · 2024Review
- Coupling of Alzheimer's Disease Genetic Risk Factors with Viral Susceptibility and Inflammation.Aging and disease · 2024Review
- A probabilistic knowledge graph for target identification.PLoS computational biology · 2024Article
- Uncloaking the viral glycocalyx: How do viruses exploit glycoimmune checkpoints?Advances in virus research · 2024Review
- Host and HBV Interactions and Their Potential Impact on Clinical Outcomes.Pathogens (Basel, Switzerland) · 2023Review
- Inhibition of SARS-CoV-2-mediated thromboinflammation by CLEC2.Fc.EMBO molecular medicine · 2023Article
- Role of Siglecs in viral infections: A double-edged sword interaction.Molecular aspects of medicine · 2023Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic hepatitis B (CHB) infection is rarely eradicated by current antiviral nucleos(t)ide analogues. We found that α2,6-biantennary sialoglycans of HBV surface antigen (HBsAg) bound human SIGLEC-3 (CD33) by IP and ELISA, and the binding affinity between SIGLEC-3 and α2,6-biantennary sialoglycans was determined by biolayer interferometry (equilibrium dissociation constant [KD]: 1.95 × 10-10 ± 0.21 × 10-10 M). Moreover, HBV activated SIGLEC-3 on myeloid cells and induced immunosuppression by stimulating immunoreceptor tyrosine-based inhibitory motif phosphorylation and SHP-1/-2 recruitment via α2,6-biantennary sialoglycans on HBsAg. An antagonistic anti-SIGLEC-3 mAb reversed this effect and enhanced cytokine production in response to TLR-7 agonist GS-9620 in PBMCs from CHB patients. Moreover, anti-SIGLEC-3 mAb alone was able to upregulate the expression of molecules involved in antigen presentation, such as CD80, CD86, CD40, MHC-I, MHC-II, and PD-L1 in CD14+ cells. Furthermore, SIGLEC-3 SNP rs12459419 C, which expressed a higher amount of SIGLEC-3, was associated with increased risk of hepatocellular carcinoma (HCC) in CHB patients (HR: 1.256, 95% CI: 1.027-1.535, P = 0.0266). Thus, blockade of SIGLEC-3 is a promising strategy to reactivate host immunity to HBV and lower the incidence of HCC in the CHB patient population.
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