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Downregulated HIPK2 Expression in T Cells Is Associated with Occult Hepatitis B Virus Infection
Zhi-Hua Jiang1, Mei-Lin Huang1,2, Li-Ping Hu1
1Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning 530028, China.
Microorganisms
|July 28, 2026
Summary
Occult hepatitis B infection (OBI) is often missed due to a lack of biomarkers. This study found lower HIPK2 expression in T cells of OBI patients, suggesting its potential as a diagnostic marker.
Area of Science:
- Immunology
- Virology
- Genomics
Background:
- Occult hepatitis B infection (OBI) shares transmission routes and outcomes with overt HBV infection but is often overlooked due to absent biomarkers.
- Previous research indicated OBI prevalence increases with age in individuals vaccinated at birth, yet immune cell transcriptome characteristics remained unclear.
Purpose of the Study:
- To investigate the transcriptome characteristics of immune cells in individuals with occult hepatitis B infection (OBI).
- To identify potential biomarkers for OBI detection and understand its immune cell dysregulation.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was performed on blood samples from 15 subjects categorized into OBI, inactive chronic HBsAg carrier (ICHC), and healthy control groups.
- Validation studies assessed HIPK2 expression in T cells and serum HIPK2 levels.
- Bioinformatic analysis identified differentially expressed genes (DEGs) and enriched immune-related pathways.
Main Results:
- No significant differences in T-cell subset proportions were observed among the groups.
- HIPK2 expression in T cells was significantly downregulated in the OBI group compared to both healthy controls and the ICHC group.
- TP53 was identified as playing a central role in HIPK2 function within the OBI context. Serum HIPK2 levels were also significantly lower in the OBI group.
Conclusions:
- Downregulated HIPK2 expression in T cells is a key feature associated with occult hepatitis B infection (OBI).
- HIPK2 warrants further investigation as a potential biomarker for distinguishing OBI from a healthy status.

