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Volume 14
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10.3390/microorganisms14071523
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Article

Downregulated HIPK2 Expression in T Cells Is Associated with Occult Hepatitis B Virus Infection

by
Zhi-Hua Jiang
1,
Mei-Lin Huang
1,2,
Li-Ping Hu
1,
Xue-Yan Wang
1,
Qin-Yan Chen
1,
Lu-Juan Zhang
1,
Ning Zhang
1,
Ying Huang
1,
Tim J. Harrison
3,
Ge Zhong
1,* and
Zhong-Liao Fang
1,*
1
Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning 530028, China
2
School of Preclinical Medicine, Guangxi Medical University, Nanning 530021, China
3
Division of Medicine, University College London Medical School, London WC1E 6BT, UK
*
Authors to whom correspondence should be addressed.
Microorganisms 2026, 14(7), 1523; https://doi.org/10.3390/microorganisms14071523
Submission received: 2 June 2026 / Revised: 9 July 2026 / Accepted: 10 July 2026 / Published: 12 July 2026
(This article belongs to the Section Virology)
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Abstract

Occult hepatitis B virus (HBV) infection (OBI) has the same transmission routes and clinical outcomes as overt HBV infection. However, due to the lack of reliable biomarkers, its occurrence and potential clinical harm are often overlooked. We previously found that the prevalence of OBI increases with age among individuals vaccinated at birth, but the transcriptome characteristics of their immune cells remain unknown. In this study, fifteen subjects born between 1987 and 1993 and vaccinated perinatally were recruited. They were divided into OBI, inactive chronic HBsAg carriers (ICHC) and healthy control groups. Blood samples were drawn from each subject for scRNA-seq and subsequent validation studies. The results showed that eleven cell types and nine T-cell subsets were identified, with no significant differences in the proportions of T-cell subsets among the three groups. HIPK2 expression in T cells was downregulated 1.42-fold in the OBI group versus healthy controls (p = 2.01 × 10−69) and upregulated 1.34-fold versus the ICHC infection group (p = 9.95 × 10−61). Differentially expressed genes (DEGs) in immune-related pathways were enriched in the OBI group. TP53 plays a central role in HIPK2 function in the context of OBI. Serum HIPK2 levels were significantly lower in the OBI group than in the healthy controls (p = 0.047), but they were also significantly lower than in the ICHC infection group. In conclusion, downregulated HIPK2 expression in T cells is associated with OBI. The functional role of HIPK2 in OBI, including its role as a biomarker to distinguish OBI from a healthy status, warrants further investigation.
Keywords: hepatitis B virus; occult HBV infection; HIPK2 gene; downregulated expression hepatitis B virus; occult HBV infection; HIPK2 gene; downregulated expression

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MDPI and ACS Style

Jiang, Z.-H.; Huang, M.-L.; Hu, L.-P.; Wang, X.-Y.; Chen, Q.-Y.; Zhang, L.-J.; Zhang, N.; Huang, Y.; Harrison, T.J.; Zhong, G.; et al. Downregulated HIPK2 Expression in T Cells Is Associated with Occult Hepatitis B Virus Infection. Microorganisms 2026, 14, 1523. https://doi.org/10.3390/microorganisms14071523

AMA Style

Jiang Z-H, Huang M-L, Hu L-P, Wang X-Y, Chen Q-Y, Zhang L-J, Zhang N, Huang Y, Harrison TJ, Zhong G, et al. Downregulated HIPK2 Expression in T Cells Is Associated with Occult Hepatitis B Virus Infection. Microorganisms. 2026; 14(7):1523. https://doi.org/10.3390/microorganisms14071523

Chicago/Turabian Style

Jiang, Zhi-Hua, Mei-Lin Huang, Li-Ping Hu, Xue-Yan Wang, Qin-Yan Chen, Lu-Juan Zhang, Ning Zhang, Ying Huang, Tim J. Harrison, Ge Zhong, and et al. 2026. "Downregulated HIPK2 Expression in T Cells Is Associated with Occult Hepatitis B Virus Infection" Microorganisms 14, no. 7: 1523. https://doi.org/10.3390/microorganisms14071523

APA Style

Jiang, Z.-H., Huang, M.-L., Hu, L.-P., Wang, X.-Y., Chen, Q.-Y., Zhang, L.-J., Zhang, N., Huang, Y., Harrison, T. J., Zhong, G., & Fang, Z.-L. (2026). Downregulated HIPK2 Expression in T Cells Is Associated with Occult Hepatitis B Virus Infection. Microorganisms, 14(7), 1523. https://doi.org/10.3390/microorganisms14071523

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