Characterisation of signalling cascade by HBV genotypes in Hepatocellular Carcinoma progression

Abstract

Background Hepatitis B virus (HBV) genotypes have different clinical outcomes in the progression of hepatocellular carcinoma. The HBV encodes two regulatory proteins, the LHBs and the HBx. Methods We analysed the impact of the HBV genotypes A-D and G (GTA-GTG) regulatory proteins on the activation and induction of the Raf-MEK-MEK, Nrf2, NF‐κB and -taxilin pathways. Results We observed a genotype-specific activation and induction of the signalling pathways by the HBV genotypes regulatory proteins, which reflects differences in the impact of the HBV genotypes regulatory proteins and the progression of HCC in respect to the HBV genotypes. The cellular compartmentalization of the HBV regulatory proteins differs among the genotypes, which case impacts on the nuclei and cytosolic signals which are activated and induced. While reconstitution of HBVΔHBx with HBx revives the wildtype nature of HBV to produce viral particles, the produced viral particles of the reconstituted HBVΔHBx are not infective. Conclusion: Differences in the activation and induction of signalling pathways may result in the observed genotype-specific immunogenicity and pathogenesis of HBV genotypes.