Host-viral interaction of HBV infection revealed by single-cell transcriptome jointly profiling the viral replication state - PubMed
4 hours ago
- #single-cell RNA sequencing
- #HBV
- #viral replication
- Development of B-BEST, a targeted sc/snRNA seq approach to quantify HBV genomic regions.
- B-BEST validated in HepAD38 cells and integrated with long-read sequencing, spatial transcriptomics, and in situ hybridization.
- Revealed significant heterogeneity among HBV-positive hepatocytes in HBeAg-positive patients.
- Active viral replication linked to hepatic synthesis/metabolism and mitochondrial function with mild type I interferon response.
- Severe inflammation correlated with suppressed HBV replication.
- Long-read sequencing showed integrated HBV transcripts using host promoters, contributing to HBsAg persistence.
- Entecavir upregulated metabolic pathways; peginterferon alfa-2b induced broad spectrum antiviral programs in Hu URG mice.
- Clonal expansion of hepatocytes diluted intrahepatic viral reservoir, suggesting a proliferative dilution mechanism.
- B-BEST platform aids in understanding HBV infection heterogeneity and identifying host determinants of viral persistence.