Liver transcriptome analysis after DF-006 treatment in an HBV mouse model

A new chemical entity, DF-006, has been shown to suppress HBV replication in an AAV-HBV mouse model. DF-006 activates NF-kB signaling. In order to elucidate the mechanism of action of DF-006, specifically the genes expression stimulated in the liver that mediated its anti-HBV efficacy, we perform deep sequencing of RNA samples taken from AAV-HBV mice 4 hours after 10 μg/kg DF-006 oral administration or vehicle control. AAV-HBV mouse models were established by injecting male C57B6/J mice with 1011 vg/mouse AAV-HBV (genotype D, serotype ayw, GenBank accession number: KX449554). Dosing with DF-006 resulted in a statistically significant increase of gene expression for 1,685 genes in the liver. We performed an over-representation analysis for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and found 53 pathways were significantly enriched. The top 10 pathways included those that involved viral infection (e.g., herpes, influenza, Epstein-Barr, hepatitis B, measles) and those that involved host innate responses (TNF, osteoclast differentiation, NF-κB, toll-like receptor, RIG-I -like receptor). qPCR analysis confirmed genes that are directly or indirectly induced through NF-kB pathway and are reported before to play a role in HBV suppression. Liver mRNA profiles of AAV-HBV mice 4 hours after vehicle or 10 μg/kg DF-006 oral administration