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Updated: Feb 5, 2026

Modeling Hepatitis B Virus Infection in Non-Hepatic 293T-NE-3NRs Cells
Published on: June 5, 2020
Human hepatic cell line 5: In-vitro model for hepatic immunobiology.
Smeeta Shrestha1, Ming Yue Yeong1, Xin Yi Cheng1
1Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore.
Human Hepatocyte Line 5 (HHL-5) cells offer a promising non-cancerous in vitro model for liver disease research. These cells exhibit distinct genetic and metabolic profiles compared to hepatocellular carcinoma (HCC) cells, supporting their use in studying liver health and disease.
Area of Science:
- Hepatology and in vitro modeling
- Cell biology and genomics
- Biochemistry and metabolomics
Background:
- Hepatocellular carcinoma (HCC) poses a significant global health challenge.
- Lack of physiologically relevant in vitro models hinders understanding of early host-virus interactions and immune responses in liver disease.
- Human Hepatocyte Line 5 (HHL-5) is an immortalized hepatocyte cell line with retained liver-specific functions.
Purpose of the Study:
- To characterize the phenotypic, genetic, and metabolic features of HHL-5 cells.
- To evaluate HHL-5 cells as a non-cancerous hepatic model.
- To compare HHL-5 cells with the HCC cell line HepG2.
Main Methods:
- Morphological and phenotypic assessment
- Whole-exome sequencing for genomic analysis
- Nuclear magnetic resonance spectroscopy for metabolomic profiling
- Western blotting for protein expression analysis
Main Results:
- HHL-5 cells demonstrated smaller cell/nuclear areas and slower proliferation than HepG2 cells.
- Genomic analysis revealed immune-related pathway enrichment in HHL-5 cells versus DNA replication pathways in HepG2 cells.
- Metabolomic profiling showed oxidative profiles in HHL-5 cells, contrasting with glycolytic phenotypes in HepG2 cells.
- HHL-5 cells exhibited reduced expression of oncogenic and stress-response markers.
Conclusions:
- HHL-5 cells represent a robust non-cancerous in vitro model.
- This model is suitable for investigating liver diseases and viral infections.
- HHL-5 cells can aid in studying early events in hepatocarcinogenesis.
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