Summary
A bioRxiv preprint reports that a hepatitis B virus basal core promoter mutation increased viral activity in human-hepatocyte chimeric mice, with effects that varied by viral genotype. Analysis of human liver-tumour datasets also found distinct gene-expression profiles associated with the mutation.
A hepatitis B virus (HBV) basal core promoter mutation accelerated viral activity in human-hepatocyte chimeric mice, according to a bioRxiv preprint posted on September 23, 2026. The effect varied across HBV genotypes. The researchers also found distinct gene-expression profiles associated with the mutation in analyses of human HBV-related liver cancers.
The study compared genetically matched wild-type HBV with basal core promoter (BCP) and precore (PC) mutants of genotypes A, C and D. The viruses were generated from recombinant covalently closed circular DNA and used to infect chimeric mice carrying human liver cells. The authors then compared infection-related gene-expression patterns with HBV-associated hepatocellular carcinoma (HCC) data from The Cancer Genome Atlas (TCGA).
Viral effects depended on genotype
In the mouse experiments, the BCP mutation accelerated the rise in virus levels in the blood for genotypes A and D; the PC mutation alone did not. For genotype C, faster increases required both the PC and BCP mutations. The viral sequences remained genetically stable during the experiments.
The researchers examined genotype D variants in more detail. Compared with the other variants, the BCP mutant produced more viral DNA in the liver and greater viral protein expression. It also increased activity in cancer-related pathways, including gene transcripts associated with a subset of HBV-related HCCs.
These results point to a direct effect of the viral variant on infected liver cells in this model. They also show why findings for one HBV genotype or mutation cannot automatically be assumed to apply to others.
Tumour profiles differed in human data
In the TCGA analysis, human HBV-related tumours often contained a mixture of wild-type and mutant viral transcripts. Tumours associated with wild-type HBV and those associated with the BCP mutant had distinct transcriptional profiles, the researchers report.
The findings add a possible molecular explanation for why the BCP mutation has been associated with increased HCC risk: it may influence liver-cell activity as well as viral replication. The human-tumour analysis identifies differences in gene expression, while the mouse experiments measure viral and liver-cell responses. Together, they support the possibility of molecularly distinct HBV-related HCC subgroups, rather than showing that the mutation itself causes cancer in people.
The work is a preprint. Its experimental findings come from human-hepatocyte chimeric mice, and its human evidence comes from tumour transcriptome analysis. The study therefore describes a potential mechanism and tumour-profile association, not patient treatment outcomes.